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Disclaimer Cancer Australia does not accept any liability for any injury, loss or damage incurred by use of or reliance on the information. Cancer Australia develops material based on the best available evidence, however it cannot guarantee and assumes no legal liability or responsibility for the currency or completeness of the information. Foreword
Lung cancer is the fourth most common cancer diagnosed in both men and women in Australia and the leading cause of cancer death.
Risk factors for lung cancer: an overview of the evidence is a comprehensive, evidence-based summary of factors that affect a person’s risk of developing lung cancer, based on a systematic review of the international literature commissioned by Cancer Australia.
This overview aims to increase awareness and understanding of the key lifestyle, environmental and occupational factors that affect lung cancer risk, in addition to the role of family history. The overview also highlights factors where the evidence is either limited or inconsistent in relation to risk of lung cancer.
We anticipate the overview will be a valuable resource to support health professionals, policy makers and the community with evidence about exposure to risk factors for lung cancer, to increase understanding of those who may be at greatest risk of lung cancer, and to inform interventions to ultimately reduce the burden of lung cancer.
Helen Zorbas AO
CEO
Cancer Australia
Risk factors for lung cancer | An overview of the evidence i
Contents
Foreword i Family history 24
Executive summary v Factors with limited evidence of an association with lung cancer 25 Background 1 Consumption of red meat and What is lung cancer? 1 processed meat 25 Lung cancer in Australia 1 Alcohol consumption 26 What is a risk factor? 1 Dietary and blood cholesterol 26 How do we measure risk? 1 Exposure to birds 27 About this overview 3 Exposure to wood dust 27 What does this overview mean Physical activity 28 for individuals? 4 Glossary 29 Tobacco smoking 5 Appendix 1 Active smoking 5 International Agency for Research Passive smoking 7 on Cancer (IARC) 31
Environmental and occupational References 32 risk factors 8
Radon 8 Arsenic 10 Polycyclic aromatic hydrocarbons 12 Cadmium 13 Asbestos 14 Silica 16 Iron and steel founding 17 Nickel 18 Beryllium 20 Painting as an occupation 21 Chromium VI 22 Air pollution 23
Risk factors for lung cancer | An overview of the evidence iii Acknowledgments
Cancer Australia gratefully acknowledges the contributions to the development of Risk factors for lung cancer: an overview of the evidence from:
the Project Working Group, which provided expert guidance and direction to the project
the Joanna Briggs Institute, University of Adelaide, which was commissioned by Cancer Australia to undertake a systematic review of national and international literature regarding risk factors for lung cancer, which formed the basis of this overview
Biotext Pty Ltd, which was commissioned by Cancer Australia to summarise the findings of the systematic review and contributed technical editing and design.
Project Working Group
Mr Andrew Bowen, consumer
Professor Kwun Fong, Thoracic and Sleep Physician; Professor, School of Medicine, University of Queensland
Professor Don Iverson, Behavioural Scientist; Executive Dean, Faculty of Science, Medicine and Health, University of Wollongong
Professor Bernard Stewart, Environmental Cancer Specialist and Head, Cancer Control Program, South East Sydney Local Health District
Professor David Roder: Cancer Epidemiologist; Chair of Cancer Epidemiology and Population Health, University of South Australia Cancer Australia
Ms Sue Sinclair, General Manager, Service Development and Clinical Practice
Dr Vivienne Milch, Medical Officer
Ms Liz King, Manager, Lung Cancer
Ms Kathleen Mahoney, Senior Project Officer, Lung Cancer
Dr Rona Hiam, Clinical and Primary Care Adviser, Lung Cancer
Ms Julie Mueller, Project Manager, Lung Cancer
Funding The development of this overview was funded by the Australian Government through Cancer Australia.
iv Risk factors for lung cancer | An overview of the evidence Executive summary Tobacco smoking Active smoking In Australia, lung cancer is the fourth most common cancer in both men and women, and the fifth most Active smoking refers to smoking tobacco in any commonly diagnosed cancer overall.1 Lung cancer form, but does not include exposure to other people’s causes more deaths than any other cancer, accounting tobacco smoke (passive smoking). There is clear for 18.9% of all cancer deaths.2 A person’s chance evidence that active smoking significantly increases of developing lung cancer may be increased by a a person’s risk of developing lung cancer.4 Overall, number of factors, known as risk factors. Risk factors current smokers are approximately 9 times more likely can include behaviours (such as tobacco smoking), to develop lung cancer than people who have never chemical agents in the environment or the workplace smoked (relative risk 9.0).5 Former smokers are almost (such as asbestos, arsenic or radon) or a family history 4 times more likely to develop lung cancer than of cancer. Some risk factors are modifiable, meaning people who have never smoked (relative risk 3.9).5 The the risk can be altered by changing behaviour or length of time since quitting smoking varied among adopting safety measures. Other risk factors, such as studies of ‘former smokers’, but was at least one year age, are regarded as non-modifiable. in the studies that specified a timeframe.5 The more a person smokes, the greater their risk of developing This overview summarises the evidence for a range lung cancer. For example, men who smoke more than of factors that are associated with a person’s risk of 20 cigarettes per day are almost 14 times more likely to developing lung cancer, and is based on a systematic develop lung cancer than people who do not smoke 3 review of published scientific studies. The systematic (relative risk 13.7)5 while those who smoke fewer review examined the published research on than 10 cigarettes per day are 1.4 times more likely primary lung cancer up to April 2011 to identify any to develop lung cancer than non-smokers.5 Smoking associations between particular risk factors and lung can also interact with other lung cancer risk factors to cancer, and to determine the magnitude of each risk. further compound a person’s risk. Pleural mesothelioma, however, is not regarded as a malignant tumour of the lung in the current version of the international coding standards for cancer, and is Passive smoking not considered in this report. Passive smoking occurs when tobacco smoke is A person’s risk of developing lung cancer can be inhaled by people other than through active smoking presented as either absolute risk or relative risk. (i.e. exposure to other people’s tobacco smoke). It Absolute risk is a person’s chance of developing lung is most common in indoor settings, where smoke cancer over a specified time period, while relative may not be as easily dispersed as it is outdoors. risk describes how many times more likely a person Passive smoking does not present as pronounced a exposed to the risk factor is of developing lung cancer risk as active smoking, although the risk can still be than a person who is not exposed to the risk factor. considerable. Evidence suggests that people who are Relative risk also allows comparison of the effects exposed to passive smoking in their workplace are of different risk factors on a person’s likelihood of up to twice as likely to develop lung cancer as people 6 developing the disease. who are not exposed (relative risk 1.2–2.0). Exposure to passive smoking at home is also associated with an Relative risk can be expressed in several different ways. increase in risk of lung cancer. Women who have never All of the following expressions have the same meaning: smoked, but have partners who smoke, are 1.3 times more likely to develop lung cancer than women The relative risk is 1.5. who live with a non-smoking partner.7 The effect The risk is 1.5 times higher. on men from the smoking habits of their partners is similar, although not statistically significant—most There is a 50% greater risk. likely due to the small number of studies that are Similarly, if the relative risk is 9.0, this means that the risk available.8 There is also emerging evidence to suggest is 9 times higher in people exposed to the risk factor. that people exposed to passive smoking as children may be at increased risk of developing lung cancer In the case of most risk factors for human diseases, an as adults.4 increase in risk depends on intensity, frequency and duration of exposure, as well as other contextual factors. The interaction of these risk and contextual factors can affect the risk estimate; therefore, relative risk should be considered as indicative of a comparative risk that may vary to some extent from place to place.
Risk factors for lung cancer | An overview of the evidence v Environmental and Cadmium Cadmium is a metal that occurs naturally in the occupational risk factors Earth’s crust and in sea water, and is used in a range of industrial applications. Evidence suggests there is Radon a modest increase in risk of lung cancer associated with cadmium exposure; however, the high level Radon is a naturally occurring radioactive gas. of variability in studies makes it difficult to measure Occupational exposure to radon is most common the overall risk. It is also difficult to define the risk in uranium miners, who have been found to be of occupational cadmium exposure, although it 1.6–3.8 times more likely to develop lung cancer than appears that exposure to cadmium fumes or mist 9,10 people who are not exposed to high levels of radon. is associated with a greater risk than exposure to 11 This risk increases with increasing exposure, and cadmium dust (relative risk 2.1 compared with 0.7–1.0 12 also with smoking. There is evidence that exposure for cadmium dust).19 Cadmium can also accumulate to moderate amounts of radon in the home can in soil, particularly in areas near industrial sources also increase the risk of lung cancer, although not to of cadmium. One study suggests that people who the same extent as occupational exposure (relative are highly exposed to cadmium in their homes (as a 13 risk 1.3). result of proximity to zinc smelters) have a higher risk of developing lung cancer than people who live in Arsenic unexposed areas.20 Occupational exposure to arsenic most commonly occurs in the mining and manufacturing industries Asbestos through inhalation of particles that contain arsenic. Asbestos is a naturally occurring mineral that was Evidence suggests that occupational exposure once commonly used in building materials. The risk of to arsenic compounds in smelter workers, miners lung cancer is increased by inhaling asbestos fibres, (particularly tin and gold miners) and production particularly in high doses or over long periods of 14 workers increases the risk of lung cancer. Generally, time. Overall, people who are exposed to asbestos as a person’s risk increases with increasing levels and part of their occupation are 1.3–2.0 times more likely duration of exposure. Smoking appears to further to develop lung cancer than unexposed workers increase the risk of lung cancer in people who are (relative risk 1.3–2.0).3 There is strong evidence that 15,16 exposed to arsenic in their workplace. There is also smoking (or a history of smoking) compounds the evidence that high levels of arsenic in drinking water risk of lung cancer in people already at increased in some populations are associated with an increased risk due to their high exposure to asbestos.21 People 14,17 risk of lung cancer; however, these findings are who have asbestosis (a disease in which the lungs not generalisable to developed countries such as become inflamed and scarred as a result of exposure Australia, where concentrations of arsenic in drinking to asbestos) have a higher risk of lung cancer than water fall well within the World Health Organization’s the general population;22 their lung cancer risk is also prescribed safe levels. Studies suggest that smoking higher than that of people exposed to asbestos who further increases the risk of lung cancer after exposure do not have asbestosis.23 Results from studies on non- to arsenic in drinking water, particularly at high occupational exposure to asbestos are variable: some 14 concentrations of arsenic. studies show an increased risk and others do not.22 It is also not clear whether the type of asbestos fibre Polycyclic aromatic hydrocarbons affects the risk of lung cancer. Polycyclic aromatic hydrocarbons (PAHs) are byproducts of burning organic material, such as coal, Silica crude oil, natural gas, garbage and tobacco. Sources Silica is a term describing a group of minerals of PAHs include urban and industrial air pollution, that contain silicon and oxygen. The small dust tobacco smoke and diet. People working in particular particles formed by some types of these minerals occupations and industries may be exposed to high can be inhaled and are associated with lung cancer. levels of PAHs. Industries associated with a higher Exposure to silica can occur in a person’s occupation, risk of lung cancer from PAH exposure include coal particularly in industries such as founding, pottery, gasification, coke production and carbon black sandblasting, construction, quarrying, and clay and production (relative risk for workers in these industries glass manufacturing and processing. People who are 18 is approximately 1.2–2.0). It is not clear whether the exposed to silica are approximately 1.2–1.3 times more length of time that a person is exposed to PAHs affects likely to develop lung cancer than people who are not their risk. exposed to silica.24,25 Studies suggest that higher
vi Risk factors for lung cancer | An overview of the evidence Silica contd. Beryllium intensity and duration of silica exposure increase the Beryllium is a naturally occurring metal that is risk of lung cancer.26,27 People with silicosis (a disease found in rocks, coal, oil, volcanic dust and soil. that causes scarring of the lungs, caused by repeated Exposure to beryllium can be an occupational risk and prolonged exposure to silica) are approximately in some specialised occupations, such as mining twice as likely to develop lung cancer as people who and processing beryllium ores, manufacturing and are exposed to silica but do not have silicosis.24,25,28-30 processing beryllium alloys or compounds, or working Smoking also increases the risk of lung cancer from with metals that contain beryllium. Evidence suggests exposure to silica, and this risk increases the more a that occupational exposure to beryllium represents a person smokes.31 modest risk factor for lung cancer, and any increase in risk is dependent on a relatively high level of exposure. Iron and steel founding However, all studies of beryllium exposure included in the systematic review were of men who worked Workers in iron and steel founding (the process of in beryllium processing plants in the United States pouring molten metal into a mould to create a new between 1940 and 1970. Overall, the relative risk of shape or object) may be exposed to several risk factors developing lung cancer in these men was 1.0–1.5.38-41 for lung cancer. Overall, evidence suggests that iron In Australia today, it is unlikely that workers or people and steel foundry workers are 1.3–1.4 times more likely in their domestic environments would be exposed to develop lung cancer than people who do not work to beryllium at levels that may increase the risk of at foundries.18 Exploring particular occupations, one lung cancer.42 study found that blast furnace workers had a higher risk of lung cancer, but no significant risk elevation was linked with workers in the manufacture of coke Painting as an occupation batteries, steel mills, lamination, steel foundries, Inhalation of paint particles or fumes is associated maintenance furnaces or facilities producing coke with an increased risk of lung cancer, and people who byproducts.32,33 Studies have found that people who work with paint every day in their occupation have worked in the foundry industry for less than 10 years higher exposure than people who do not work as generally did not have a higher risk of developing lung painters. People who work in the painting trade may cancer, but people who have worked in iron and steel also be exposed to other substances, such as asbestos, founding for more than 30 years are almost twice as chromium and cadmium, that may increase their risk likely to develop lung cancer as people who do not of developing lung cancer. The combined results of work in the industry (relative risk 1.9).3 Foundry workers several studies show that, overall, people who work who smoke have a higher risk of developing lung as painters are 1.3 times more likely to develop lung cancer than foundry workers who do not smoke, and cancer than people who do not work as painters.43-46 the risk increases with increased smoking.33-35 There was inconsistent evidence regarding the impact of duration of employment as a painter or a spray Nickel painter on lung cancer risk. People who work with nickel in their occupations can be exposed to high levels of nickel through fumes, Chromium VI dust and mist. Evidence suggests that occupational Exposure to chromium VI (a toxic form of chromium) exposure to nickel represents a modest increase in the can occur in occupations that involve the production, risk of lung cancer.3 However, the variability in studies use and welding of chromium-containing alloys included in the review makes it difficult to provide (such as stainless steel and high-chromium steel); a clear, quantifiable risk. The risk of developing lung the production and use of chromium-containing cancer due to nickel exposure appears to increase with paints (such as in the aerospace, construction and increasing levels and duration of exposure.36 One study maritime industries); electroplating; catalysts; chromic found that exposure to nickel for more than 20 years acid and pesticides. Combined results of many was associated with a relative risk of lung cancer of 1.6 studies indicate that people who are exposed to compared with no exposure to nickel.36 Smokers who chromium VI are at approximately 1.2 times greater are exposed to nickel also appear to have a higher risk of lung cancer than people who are not exposed risk of developing lung cancer than non-smokers (standardised mortality rate 1.2).47 There is insufficient who are exposed to nickel, and this risk increases with evidence to determine whether duration of exposure increasing nickel exposure.37 to chromium VI affects the risk of developing lung cancer, but evidence does suggest that the amount of chromium exposure may have a greater effect on risk than duration of exposure.48
Risk factors for lung cancer | An overview of the evidence vii Air pollution Family history Air pollution in outdoor air includes fine particulate Families share environmental and behavioural matter and gases, mainly from urban pollution and characteristics as well as genetic traits, and a person’s vehicle exhaust. There is evidence that exposure to fine knowledge of a history of lung cancer within their particulate matter in the air increases a person’s risk of family can help to increase understanding of these lung cancer by 1.2 times after one year of exposure.49 shared risks. Genomic research and the application of This risk does not appear to increase over time—the genetic technologies are emerging areas of research relative risk after 21 years’ exposure to fine particulate that are increasing our understanding of cancer matter is not significantly different from the risk after biology and of the genetic factors associated with one year’s exposure.50 Sulfur dioxide and nitrogen lung cancer. There is also potential for the application dioxide (other gaseous components of air pollution) of genomic approaches to management of cancer do not appear to be associated with an increased risk risk. This systematic review, however, was limited to of lung cancer.49,51 However, there is mixed evidence as studies of family relationships. There is evidence to to whether other nitrogen oxides are associated with suggest that a person who has a family member with a small increase in risk.49,52 There has been no evidence lung cancer is approximately twice as likely to develop of an increase in lung cancer risk in studies of people lung cancer as someone without a family history of living near busy or major roads.49,51,52 the disease.53 The results suggest that the risk appears to be more significant if two or more family members have had lung cancer or if a person’s mother had lung Diesel exhaust as a risk factor for cancer.53 lung cancer
In June 2012, the International Agency for Research on Cancer (IARC) identified that there is sufficient evidence that exposure to diesel engine exhaust is associated with an increased risk of lung cancer.54 While large populations are exposed to diesel exhaust in everyday life, whether as part of their occupation or through exposure to motor vehicle and other diesel engine exhausts in the ambient air, the main studies that led to IARC’s conclusion were in highly exposed workers. Exposure to diesel exhaust is not included as a risk factor in this overview, as the systematic review was conducted before IARC’s classification of diesel engine exhaust as a substance with sufficient evidence to be causally associated with lung cancer.
viii Risk factors for lung cancer | An overview of the evidence This means that a person can be exposed to a risk Factors with limited factor, or several risk factors, and not develop lung cancer during their lifetime. On the other hand, a evidence of an association person may never have been exposed to any known with lung cancer risk factors, but they might develop lung cancer. In addition, even if a person with lung cancer has a risk Factors that have not been found to be associated factor, it is usually hard to know how much that risk with an increased risk of lung cancer, including factor contributed to the development of the cancer. where the studies are either of poor quality or have conflicting results: This overview provides consumers, health professionals and policy makers with evidence-based consumption of red meat and processed meat information about risk factors for lung cancer. By alcohol consumption understanding and recognising the risk factors, people can make informed decisions about exposure to these dietary and blood cholesterol factors. exposure to birds
exposure to wood dust Levels of evidence physical activity. For each risk factor, the inclusion and presentation of the findings has been broadly What does this mean ordered according to the National Health and Medical Research Council (NHMRC) levels of for individuals? evidence:57 The evidence discussed in this overview outlines the Level I—a systematic review of risk factors for lung cancer at a population level— Level II studies that is, the evidence is based on averages from large groups of people. The relative risks describe the Level II—a prospective cohort study probability of developing lung cancer in a certain group of people over a certain period of time, but they Level III-1—an ‘all or none’ study cannot tell us which individual person might develop Level III-2—a retrospective cohort study lung cancer. Level III-3—a case–control study
Level IV—a cross-sectional study or case series.
These levels of evidence for the risk factors are shown in the summary of relative risks table (page x - xi) and in the risk graphics shown for each of the risk factors in this overview.
Risk factors for lung cancer | An overview of the evidence ix Summary of relative risks
Active smoking
Radon
Arsenic
Polycyclic aromatic hydrocarbons
Cadmium
Asbestos
Silica
x Risk factors for lung cancer | An overview of the evidence Summary of relative risks cont.
Passive smoking
Family history
Iron and steel founding
Nickel
Beryllium
Painting as an occupation
Chromium VI
Air pollution
Risk factors for lung cancer | An overview of the evidence xi
Symptoms of lung cancer can often be vague and Background non-specific, which can hinder early diagnosis and treatment.62 Although survival rates have gradually increased since 1982, they remain poor, with about 14% of people diagnosed likely to be alive five years What is lung cancer? after their diagnosis.63 Poor survival is due at least in part to the relatively high proportion of people Lung cancer is a disease where cells in the lungs diagnosed at an advanced stage, when the cancer has become abnormal and grow out of control, forming already spread to other parts of the body and is difficult a malignant tumour, or cancer. As the cancer grows, to treat successfully. Poor survival outcomes for people it can impair lung function and spread to other parts with lung cancer are reflected internationally.61 of the body through a process known as metastasis. There are different types of lung cancer, beginning The risk of developing lung cancer increases with age. in different types of cells in the lungs. Of all lung In 2009, 85% of new lung cancers in men and 81% in cancers diagnosed in 2007, non–small cell carcinoma women were diagnosed in people aged 60 years or (i.e. squamous cell carcinoma, adenocarcinoma and older.64 In 2009, the average age of first diagnosis was large cell carcinoma) represented 64% of lung cancers 71 years for men and 70 years for women.59 Overall, in males and 61% in females, small cell carcinoma about 1 in 13 men and 1 in 22 women in Australia represented 11% of lung cancers in males and 13% in will be diagnosed with lung cancer by the age of 85.59 females, and other types of lung cancer accounted for However, people’s behaviours, occupations or family the remaining 25% of lung cancer cases.1 histories can affect their risk of developing lung cancer.
In this overview, lung cancer refers to all forms of primary lung cancer but does not include pleural What is a risk factor? mesothelioma, which is a rare type of cancer affecting the membrane that covers and protects the lungs A risk factor is any factor that is associated with an (the pleura). Pleural mesothelioma is almost always increase in someone’s chances of developing a caused by exposure to asbestos.58 Because pleural certain condition, such as cancer. Some risk factors mesothelioma occurs in the lining of the lung, it is are modifiable, such as lifestyle or environmental risk sometimes referred to as lung cancer. However, pleural factors, and others cannot be modified, such as family mesothelioma is not regarded as a malignant tumour history and inherited factors. of the lung in the current version of the international coding standards for cancer and is not considered in this overview.1 Cancer that originated in other parts How do we measure risk? of the body can also spread to the lungs, but these Risk factors may also be called hazards. The extent of secondary cancers are not classified as lung cancer harm from the risk factor and the consequences of this and are not included in this overview. harm are expressed in terms of how hazardous the risk factor is (i.e. its potential to cause harm). However hazardous a risk factor is, it will only pose a threat Lung cancer in Australia when other factors combine to allow a person to be In Australia, lung cancer is the fourth most common exposed to it. ‘Risk’ measures the likelihood of harm cancer diagnosed in both men and women, and the associated with exposure to the hazard. fifth most commonly diagnosed cancer overall.1 In 2009, In the case of most risk factors for human diseases, 8.9% of all new cancers were lung cancers, with 10 193 an increase in risk depends on both the intensity of people diagnosed (6034 men and 4159 women).59 Men exposure (how much of the risk factor a person is are almost twice as likely to be diagnosed with lung exposed to at one time) and the frequency or duration cancer as women;60 however, since 1982, the rate of of exposure (how often and for how long a person is lung cancer in men has been decreasing, while the rate exposed to the risk factor over their lifetime). in women has been increasing.1 Lung cancer causes more deaths in Australia than any Absolute risk other cancer.2 A total of 8099 Australians died from lung cancer in 2010 (4934 men and 3165 women), Absolute risk is a person’s chance of developing comprising nearly 19% of all cancer deaths.1,2 Since a specific disease over a particular period of time. 1982, mortality rates for lung cancer have decreased A person’s absolute risk of disease is estimated by in men, but increased in women.59 Worldwide, lung examining a large number of people similar in some cancer is the leading cause of cancer death, accounting respect (such as age or gender) and counting the for more than 1.37 million deaths per year.61 number of individuals in this group who develop the disease within a defined period.
Risk factors for lung cancer | An overview of the evidence 1 Absolute risk contd. develop the disease, even though they have never been exposed to that risk factor. Relative risk indicates For example, the risk of developing lung cancer by the how many times more likely a person in the exposed age of 85 years for an Australian man is 1 in 13 and group is to develop the disease. Importantly, for a for an Australian woman is 1 in 22. This means that for disease such as lung cancer, relative risk also allows every 13 men who live to 85, one of them will have comparison of the effects of different risk factors on a been diagnosed with lung cancer during his lifetime, person’s likelihood of developing the disease. and, similarly, for every 22 women who live to 85, one of them will have been diagnosed with lung cancer In mathematical terms, relative risk is the absolute during her lifetime.59 risk in the exposed group divided by the absolute risk in the unexposed group. If the relative risk is 1, Absolute risk is a measure of the size of the risk this indicates that the exposed group has the same outcome overall. This can be useful to understand chance of developing the disease as the unexposed the importance of a risk factor and to make decisions group. If the relative risk is greater than 1, the exposed about exposure to it. group is at greater risk, and if the relative risk is less than 1, the exposed group has a lower risk than the Relative risk unexposed group. Relative risk compares the absolute risk of a group Relative risk can be expressed in several different ways. of people who are exposed to a risk factor with the The following expressions all have the same meaning: absolute risk of a group of people who are not exposed The relative risk is 1.5. to the risk factor. For example, you could compare the The risk is 1.5 times higher. risk of lung cancer in people who smoke with the risk There is a 50% greater risk. of lung cancer in people who do not smoke. Similarly, if the relative risk is 9.0, this means that the This is an important distinction, because a certain risk is 9 times higher. proportion of people in the unexposed group will also
Figure 1 Calculating relative risk
2 Risk factors for lung cancer | An overview of the evidence Relative risk contd. The International Agency for Research on Cancer (IARC) Monographs on the Evaluation of Carcinogenic In the case of most risk factors for human diseases, Risks to Humans published to 2011 were used as a an increase in risk depends on intensity, frequency main source of evidence and guided the identification and duration of exposure, as well as other contextual of risk factors to be studied in this overview (see factors. The interaction of these parameters can Appendix 1 for more detail of IARC classifications of risk affect the precision of the risk estimate; therefore, the factors). In addition, a multidisciplinary expert advisory relative risk should be considered as an indication of group assisted in the prioritisation of risk factors to be how to interpret the evidence in the context of these studied. In guiding this process, the group considered parameters, not as a definitive measurement. the likelihood of exposure to respective risk factors in In this overview, relative risk is reported to one Australia, the likely population exposures to these risk decimal place. This is usually accompanied by factors, the likely risks associated with these exposures, a 95% confidence interval (95% CI), which is a the quality of available evidence from which to draw measure of the precision of the risk estimate robust conclusions, and the potential for modifiability. (i.e. the extent to which it is likely to vary by This overview refers to cancers other than lung cancer chance)—the narrower the interval, the more where IARC has identified that there is sufficient precise the estimate of the risk, and the less likely evidence of a causal relationship between exposure to that the risk would be subject to chance variation. the agent and those cancers. Most studies reported risks as relative risks. If risks were expressed as odds ratios, standardised mortality ratios About this overview or another estimate of risk or effect, this is specified in the text of this overview, but these measures were This overview provides consumers, health interpreted similarly to relative risks (see the systematic professionals and policy makers with evidence- review for more details). A glossary of terms, including based information about risk factors for lung cancer. odds ratios and standardised mortality ratios, is Understanding and recognising these risk factors can provided at the end of this overview. help people make informed decisions about their exposure to these factors.
Data sources This overview is a summary of the systematic review conducted for Cancer Australia by the Joanna Briggs Institute at the University of Adelaide. The systematic review is available on the Cancer Australia website at www.canceraustralia.gov.au. The systematic review examined the published research on lung cancer up to April 2011, to identify any associations between particular risk factors and lung cancer, and to determine the magnitude of each risk. In the systematic review, the level of evidence available was assessed for each risk factor, using the National Health and Medical Research Council (NHMRC) levels of evidence for aetiology.57
Level I - a systematic review of Level II studies Level II - a prospective cohort study Level III-1 - an 'all or none' study Level III-2 - a retrospective cohort study Level III-3 - a case-control study Level IV - a cross-sectional study or case series
Risk factors for lung cancer | An overview of the evidence 3 Presentation of relative risk estimates The systematic review examined published research of studies of relative risk and other measures of association on risk factors for lung cancer. These studies were conducted in numerous contexts across various population groups and with a mixture of methodologies to explore the impact of exposure to the risk factor and the potential impact of tobacco smoking status on relative risk for lung cancer for that risk factor. For some risk factors, the systematic review identified a wide range of heterogeneous data (i.e. a high level of variability between studies). In some cases, the authors drew on published meta-analyses to determine overall relative risk estimates, and, in others, the authors conducted their own meta-analysis of studies to synthesise findings.
The risk estimates represented in the risk graphics at the top of each of the risk factors in this overview reflect the synthesised findings as identified in the systematic review. More details pertaining to the range of the relative risks identified are summarised in the body of the overview. The risk graphic also identifies the risk factors where tobacco smoking interacted with that risk factor to increase lung cancer risk.
What does this overview mean for individuals? The evidence discussed in this overview outlines the risk factors for lung cancer at a population level— that is, the evidence is based on averages from large groups of people. The relative risk describes the probability of developing lung cancer of a group of people that share a particular risk factor, compared with those without this risk factor. Information about risk factors cannot predict whether an individual person will actually develop lung cancer.
This means that a person can be exposed to a risk factor, or several risk factors, and not develop lung cancer during their lifetime. On the other hand, a person may never have been exposed to any known risk factors but still develop lung cancer. In addition, even if a person with lung cancer has a risk factor, it is usually hard to know how much that particular risk factor contributed to the development of the cancer.
4 Risk factors for lung cancer | An overview of the evidence Tobacco smoking
Active smoking
Active smoking refers to smoking tobacco through followed by an appreciable decline in the smoking any means, including cigarettes, cigars, pipes, bidis rate from 31% in 1980 to 14% in 2011–12.1,65 Decreases and waterpipes. It does not include exposure to in smoking rates have occurred across all age groups, other people’s tobacco smoke (known as passive and particularly among people aged less than smoking), which is addressed as a separate risk factor 45 years.65 in this overview.
IARC has identified that there is sufficient evidence What is the risk? to indicate that tobacco smoking is a cause of lung cancer.4 In Australia, about 90% of lung cancer in Overall risk males and 65% in females is estimated to be a result of There is clear evidence that active smoking active smoking.1 IARC has also identified that there is significantly increases a person’s risk of developing sufficient evidence to indicate that tobacco smoking lung cancer. Current smokers are approximately can cause cancer of the oral cavity, nasopharynx, 9 times more likely to develop lung cancer than oropharynx and hypopharynx, nasal cavity and people who have never smoked (relative risk 9.0, accessory sinuses, larynx, oesophagus, stomach, 95% CI 6.7–12.1).5 Although the risk of lung cancer pancreas, colorectum, liver, kidney (body and pelvis), is lower for former smokers than active smokers, ureter, urinary bladder, uterine cervix and ovary it remains significant, with former smokers almost (mucinous), and myeloid leukaemia, and that parental 4 times more likely to develop lung cancer than smoking is a cause of hepatoblastoma in children.4 people who have never smoked (relative risk 3.9, Also, IARC has identified a positive association 95% CI 2.8–5.3).5 The length of time since quitting between tobacco smoking and breast cancer risk smoking varied among studies of ‘former smokers’, but in women.4 was at least one year in the studies that specified a timeframe.5 Exposure to active smoking The more a person smokes, the greater their risk of In 2011–12, one in six (16.3%) Australians aged developing lung cancer. In males, for example, a 18 years and over smoked tobacco daily (about meta-analysis found that those men who smoke fewer 2.8 million people).65 A further 2% reported that they than 10 cigarettes per day are 1.4 times more likely to smoked tobacco less than daily, and 31% reported that develop lung cancer than non-smoking men (relative they were ex-smokers. risk 1.4, 95% CI 1.3–1.5).5 This relative risk increases to 2.7 (95% CI 2.1–3.4) for men who smoke 10–19 In Australia, the smoking rate has declined since the cigarettes per day, and 13.7 (95% CI 7.4–25.5) for men second half of the last century. In 1964, an estimated who smoke more than 20 cigarettes per day.5 Similarly, 58% of males smoked, with this decreasing to 18% women who smoke fewer than 10 cigarettes per day in 2011–12. For females, the overall smoking rate are 1.5 times more likely to develop lung cancer than increased slightly in the 1960s and 1970s, which was
Risk factors for lung cancer | An overview of the evidence 5 Overall risk contd. non-smoking women (relative risk 1.5, 95% CI 1.4–1.6). This relative risk increases to 3.3 (95% CI 2.6–4.2) for women who smoke 10–19 cigarettes per day and 24.1 (95% CI 12.7–45.9) for women who smoke more than 20 cigarettes per day.5 Despite these apparent differences in risk between the sexes, there is insufficient evidence overall to determine whether women have a higher risk of developing lung cancer from smoking than men.5
Overall, the relative risk of lung cancer increases by 0.07, or 7%, for each additional cigarette smoked per day (relative risk 1.07, 95% CI 1.06–1.08).5
The length of time that a person has been smoking is likely to affect their risk of developing lung cancer. However, because individual studies categorised the length of time that people smoked in different ways, the results cannot be combined to determine the relative risks for smoking for different lengths of time.5
Risk from other forms of tobacco smoking People who smoke mentholated cigarettes have the same relative risk of developing lung cancer as people who smoke non-mentholated cigarettes.66
Studies that investigated the risk of lung cancer from smoking a waterpipe (also known as an arguileh, hookah, narghile or shisha) were generally of poor quality. However, overall they indicate that smoking a waterpipe increases the risk of lung cancer (relative risk 2.1, 95% CI 1.3–3.4).67
Interaction with other risk factors for lung cancer Smoking is not only a risk factor for lung cancer in itself, but can also interact with other risk factors to further compound the risk. For example, studies suggest that smokers and former smokers who are occupationally exposed to radon have a higher risk of developing lung cancer than from exposure to either radon or smoking alone. Evidence also suggests that smoking has an additive effect on the risk of developing lung cancer due to exposure to asbestos, arsenic, occupational radon, polycyclic aromatic hydrocarbons, silica, nickel, a positive family history, and iron and steel founding. See the relevant risk factors in this overview for details.
6 Risk factors for lung cancer | An overview of the evidence Passive smoking
Passive smoking is also known as involuntary smoking, are exposed to 45 years of passive smoking in the exposure to environmental tobacco smoke or second- workplace are approximately 1.6 times more likely to hand smoke, and tobacco smoke pollution. It occurs develop lung cancer than people who have not been when tobacco smoke is inhaled by a person other exposed (relative risk 1.6, 95% CI 1.5–1.8).6 than through active smoking (i.e. exposure to other people’s tobacco smoke). Exposure in the household IARC has identified that there is sufficient evidence Most studies on passive smoking as a result of to indicate that passive smoking is a cause of exposure to smoke from another person in the lung cancer.4 household involve women who have never actively smoked but are exposed to passive smoke from their Exposure to passive smoking partners. In one analysis, 45 out of 55 studies (82%) showed that non-smoking women who lived with a Passive smoking is most common in indoor settings, partner who smoked were more likely to develop lung where smoke may not be as easily dispersed by the air cancer than women who lived with a non-smoking as it is outdoors. Before smoking bans were introduced partner, with an overall relative risk of 1.3 (95% CI 1.2– in indoor public places, smoking was permitted in 1.4).7 The effect on men from the smoking habits of restaurants, bars and a variety of other indoor areas. their partners was similar, although not statistically People who visited or worked in these places may significant—most likely due to the small number of have been exposed to passive smoking. Exposure can studies that contributed data.8 also occur in the home—for example, if one or more people in a household smoke but others do not. Exposure from parents during childhood The systematic review found that there was little What is the risk? evidence to suggest that exposure to tobacco smoke during childhood increases the risk of lung cancer Workplace exposure in adulthood. An analysis of 11 studies found little Passive smoking does not present as pronounced evidence of increased risk of lung cancer, regardless of a risk as active smoking, although the risk can be which parent smoked.68 However, IARC has identified significant. Evidence suggests that people who are that there is emerging evidence to suggest that exposed to passive smoking in their workplace are exposure to second-hand smoke among children may 1.2 times more likely to develop lung cancer than increase the risk of lung cancer in adulthood.4 people who are not exposed in their workplace (relative risk 1.2, 95% CI 1.2–1.3).6 This relative risk increases to 2.0 (95% CI 1.3–2.6) for people who are highly exposed to passive smoking in the workplace.6 However, it is difficult to define what exactly constitutes ‘high’ workplace exposure, as the highest exposure categories varied significantly among studies included in the meta-analysis.6
The length of time a person is exposed to passive smoking also affects their risk of developing lung cancer. Analysis of data suggests that people who
Risk factors for lung cancer | An overview of the evidence 7 Environmental and occupational risk factors
Radon
Radon is a naturally occurring radioactive gas What is the risk? that forms underground and disperses into the atmosphere. It decays naturally into particles that can attach to dust and other aerosols. If these particles Occupational radon exposure are inhaled, they can deposit in the lungs and expose Many studies of occupational exposure to radon use a person to radiation.69 This can cause a variety the ‘working level month’ (WLM) as a way of measuring of damage to cells and DNA that can contribute the length of time a person is exposed to radon, and to cancer.70 the dose of radiation they were exposed to. A ‘working level’ is a defined amount of radiation, and a WLM IARC has identified that there is sufficient evidence to refers to exposure to a working level of radiation for 70 indicate that radon is a cause of lung cancer. 170 hours (the typical working month).
Evidence suggests that uranium miners are at risk of Exposure to radon developing lung cancer from radon exposure. Risk in Radon exposure can occur during a person’s these miners increases in a dose-dependent manner occupation, particularly uranium miners. Radon forms with increased levels of exposure. Studies in Europe from the radioactive decay of uranium, and is therefore showed that uranium miners with exposure of common in uranium mines. In 2011, approximately 40–240 WLM had a relative risk of developing lung 8000 Australians were employed in the uranium cancer of 1.6–3.8.9,10 Another study showed that this mining and milling industry in occupations with a risk risk increased to 4.6 (95% CI 2.3–9.4) at exposures of of radiation exposure.71 The radiation doses of these more than 1000 WLM.11 workers are assessed and recorded regularly by their employers, and entered in the Australian National Other types of miners can also be exposed to radon. Radiation Dose Register.71 Iron ore miners have a higher risk of developing lung cancer due to radon exposure than the general Radon forms part of the natural background population, although generally not to the same extent radiation on Earth, and all people are exposed to as uranium miners.70 However, studies informing the extremely small amounts of it. The radon level in any risk of lung cancer in iron ore miners were conducted particular place in the world depends on the nature in Sweden, the United States, the United Kingdom and of the underlying rock and soil; therefore, radon China, with no included studies conducted in Australia. exposure in Australia will be different from that in other countries.72,73 Because radon can accumulate in enclosed spaces, including houses, residential exposure to radon can be substantial—although levels in Australia are lower than in many other countries.72 The average radiation level in homes in Australia is 11 becquerels per cubic metre (Bq/m3), but levels can range from 1 to more than 400 Bq/m3.72,73
8 Risk factors for lung cancer | An overview of the evidence Occupational radon exposure contd.
Effect of smoking Studies suggest that smokers and former smokers who are occupationally exposed to radon have a higher risk of developing lung cancer than from radon exposure or smoking alone. In particular, evidence shows that uranium miners who smoke increase their lung cancer risk by approximately 7 times.3,12 The relative risk of lung cancer for people who have never smoked increases with increasing radon exposure; however, these risks are consistently higher in former smokers, and even higher in current smokers.12
Residential radon exposure There is evidence that residential exposure to radon increases a person’s risk of developing lung cancer, although generally not to the same extent as occupational exposure. Most studies of exposure to radon in the home measure the radon concentration in Bq/m3 over 5 to 30 years, rather than the occupational measure of WLM.
Various syntheses of studies from different continents suggest that people exposed to radon concentrations of more than 250 Bq/m3 are 1.4 times more likely to develop lung cancer than unexposed populations (relative risk 1.4, 95% CI 1.2–1.7).13
Studies in Europe have estimated that residential radon exposure increases the risk of lung cancer by 8% for every 100 Bq/m3 of radon exposure over 5 to 30 years.70
Effect of smoking There is evidence to suggest that the risk of developing lung cancer from residential exposure to radon may also be increased by smoking, although not to the same extent as in miners. One study shows that, for smokers and non-smokers exposed to the same radon concentration (100 Bq/m3) for at least five years in China, the relative risk increases with the number of cigarettes smoked per day. People who smoked 10 cigarettes per day over 30 years had a risk of 2.9 (odds ratio, 95% CI 2.2–4.0), while people who smoked 20 cigarettes per day over 40 years had a relative risk of 4.5 (95% CI 2.8–7.1).74 Another study suggests that people living in homes in Sweden with environmental tobacco smoke and a radon concentration of 140 Bq/m3 have a relative risk of developing lung cancer of 2.1 (95% CI 1.2–3.7).75
Risk factors for lung cancer | An overview of the evidence 9 Arsenic
Arsenic is a chemical found in the Earth’s crust. It can What is the risk? contaminate air, water and soil as a result of natural causes (such as volcanic activity) or human activities Evidence suggests that occupational exposure (such as mining, smelting and burning fuel).14 Arsenic to arsenic compounds in smelter workers, miners can enter the body through contaminated food, water (particularly tin and gold miners) and in production or air.14 It is thought that the arsenic reacts in the body workers increases the risk of developing lung cancer, to form free radicals, which can damage cells and DNA, with an overall risk resulting from occupational and contribute to cancer.14 exposure to arsenic and its compounds of 1.5–1.7.3
IARC has identified that there is sufficient evidence to Generally, the greater a person’s cumulative exposure indicate that arsenic and inorganic arsenic compounds to arsenic, the higher their risk of developing lung are a cause of lung cancer. IARC has also identified that cancer, with risk elevated two- to threefold with there is sufficient evidence to indicate that inorganic greater levels of exposure and longer duration of arsenic compounds can cause cancer of the urinary exposure to arsenic i.e. longer duration of employment bladder and skin.14 ranging between 10 and 40 years (relative risk 2.0-3.0).3
Exposure to arsenic Exposure by inhalation People most commonly exposed to arsenic are those Smelter workers and people living near smelters who work in the mining and metal-manufacturing industries.76 Workers in the manufacture of agricultural Smelter workers may have an increased risk of chemicals, dyestuffs, pharmaceuticals and wood developing lung cancer from arsenic exposure, preservatives, and the mining, metallurgical, glass- although a precise estimate of the risk cannot making and semiconductor industries can also be calculated because the studies varied in their be exposed.14,77 methods of measuring exposure. Relative risks in most studies increase with exposure to higher levels of Occupational exposure usually occurs by inhalation arsenic, up to a relative risk of 3.7 (95% CI 2.1–6.4) for of particles that contain arsenic in industrial facilities smelter workers exposed to high levels for more than such as smelters; coal-burning power plants; and 10 years.14 battery-assembly, glass-manufacturing and electronics facilities.14 It is possible that people who live near these The evidence of lung cancer risk for people living industrial facilities may be exposed to arsenic in the air. near smelters or other arsenic-producing industrial facilities is inconclusive because of the limited number Arsenic exposure can also occur through of studies and mixed results from those studies that contaminated drinking water. This is more common in are available.15,78 developing countries, where arsenic contamination of water can be high.14
10 Risk factors for lung cancer | An overview of the evidence Exposure by inhalation contd.
Other occupational exposures Studies have investigated the risk of developing lung cancer or dying from lung cancer in production workers at a fertiliser plant, nickel refinery workers, stokers and pesticide manufacturers. Two studies showed that these workers were more likely to develop lung cancer due to their exposure to arsenic than unexposed people.14 The risk of lung cancer increased with increasing duration of employment.14
Effect of smoking Smoking appears to interact with arsenic exposure to further increase the risk of developing lung cancer, particularly for smelter workers and metal miners.15,16
Exposure by ingestion The World Health Organization (WHO) recommends that drinking water should not contain more than 0.01 milligrams of arsenic per litre (mg/L). In Australia, prescribed safe levels of arsenic in drinking water are set at a maximum of 0.007 mg/L.76
Based on data from studies conducted in some parts of Japan, Chile and Taiwan, there is evidence that high levels of arsenic in drinking water are associated with an increased risk of lung cancer.14,17 However, these findings are not generalisable to developed countries such as Australia, where concentrations of arsenic in the drinking water are well within the prescribed safety levels.
Effect of smoking Studies suggest that smoking further increases the risk of lung cancer after exposure to arsenic in drinking water, particularly at high concentrations of arsenic.14
Risk factors for lung cancer | An overview of the evidence 11 Polycyclic aromatic hydrocarbons
Polycyclic aromatic hydrocarbons (PAHs) are relative risk for people in the carbon black production byproducts of burning organic material, such as coal, industry was 1.3 (95% CI 1.1–1.6).18 crude oil, natural gas, garbage and tobacco.18,79 PAHs can enter the body through the skin, respiratory tract Aluminium production workers may also be at and digestive tract, where they are slowly absorbed by increased risk of developing lung cancer from PAH cells and cause DNA damage, which can contribute exposure, although the variation in results of reported to cancer.80 studies is large. Two studies showed no significant increase in risk;18,82 however, analysis of two other IARC has identified that there is sufficient evidence to large studies83,84 showed a relative risk of 2.2 (95% CI indicate that various occupational exposures to PAHs 1.5–3.1).3 These differences may be attributable to are a cause of lung cancer.80,81 As well as lung cancer, different levels of exposure or different processes in IARC identified that these exposures can cause cancer different countries. of the bladder and skin.80,81 There is inconsistent evidence for an association between exposure to PAH and lung cancer for Exposure to polycyclic aromatic workers employed in coal tar distillation, creosote hydrocarbons production, carbon black production and carbon electrode manufacture.18 Apparent variations in study Sources of PAHs include tobacco smoke, urban and results of risk across industries are also affected by industrial air pollution, and diet. People working in limitations of the data, including the small number particular occupations and industries may be exposed of studies and the lack of standardised methods to 80 to high levels of PAHs. PAH exposure usually includes measure exposure. a mixture of different PAHs, but benzo-a-pyrene (BaP, a common PAH) is often measured as a marker of Studies on cumulative PAH exposure do not show a general PAH exposure.18,80 clear relationship between PAH exposure and the risk of developing lung cancer over time. What is the risk? The risk of developing lung cancer associated with Evidence suggests that occupational exposure to PAHs PAH exposure appears to increase in smokers; however, the evidence is inconclusive because of in various industries, particularly coal gasification, coke 3,83-85 production and potentially aluminium production, limitations in the available studies. increases the risk of developing lung cancer. Overall, increases in risk ranged from 1.2 to 2.3 times for people exposed compared with those not exposed.3
The risk of developing lung cancer due to PAH exposure varies across different industries. For example, one meta-analysis reported that people exposed to PAHs in the coal gasification industry were 2.3 times more likely to develop lung cancer than workers not exposed to PAHs in the industry (relative risk 2.3, 95% CI 2.0–2.6). Similarly, people exposed to PAHs in the coke production industry were 1.6 times more likely to develop lung cancer than unexposed workers (relative risk 1.6, 95% CI 1.5–1.7), while the
12 Risk factors for lung cancer | An overview of the evidence Cadmium
Cadmium is a metal that occurs naturally in the Earth’s Occupational exposure crust and in sea water. It is used in a range of industrial applications, including manufacture of nickel–cadmium In Australia, the risk of harmful cadmium exposure is batteries, pigments, coatings and plating, stabilisers low. There are guidelines in place to limit industrial for plastics, alloys, semiconductors and solar panels.86 emissions of cadmium and to limit cadmium exposure Cadmium is also an impurity in non-iron metals, steel, in the workplace. 86 fossil fuels, cement and phosphate fertilisers. It is difficult to define the risk of occupational Cadmium is released into the air from erosion of cadmium exposure. Several studies of people who cadmium-containing rocks, sea spray and bushfires. were exposed to cadmium in their occupations for Industrial sources include mining and smelting zinc, at least one year showed that the risk of developing burning fossil fuels, incinerating waste and producing lung cancer compared with the risk in people who cement. Cadmium does not break down in the had never been exposed to cadmium, or compared environment and can accumulate over time, especially with the general population, appeared to be elevated, 19,36,86 in or near industrial areas.87 but results were not statistically significant. These studies were constrained by the small numbers IARC has identified that there is sufficient evidence to of workers who had been highly exposed and had indicate that cadmium is a cause of lung cancer.86 worked long term, the lack of historical data on exposure, and difficulties defining and measuring Exposure to cadmium cumulative exposure across studies. Industries with the highest potential for occupational Cadmium fumes or mist contain smaller particles than cadmium exposure include cadmium production cadmium dust, which may be more easily absorbed and refining, nickel–cadmium battery manufacturing, through the lungs. One study suggests that exposure cadmium pigment manufacturing, cadmium alloy to cadmium fumes or mist at high levels or for a long production, mechanical plating, zinc smelting, duration has a higher risk than exposure to cadmium cadmium–silver alloy soldering, and polyvinyl chloride dust (relative risk 2.1, compared with 0.7–1.0 for cadmium 19 (PVC) compounding. Occupational exposure to dust), although the trend was not statistically significant. cadmium has decreased since the 1970s, and many countries enforce regulations that restrict its use. Residential exposure Because cadmium does not break down in the People who do not work with cadmium can be environment, it can also accumulate in soil, particularly exposed to it through the air, food and contaminated in areas near industrial sources of cadmium. One study 88 dust. Smoking is also a source of cadmium exposure. of people living in an area of Belgium near three zinc smelters, where there were high levels of cadmium What is the risk? in the soil, found that they were 3.6 times more likely to develop lung cancer than people who lived in Overall, the evidence suggests that there is a unexposed areas (relative risk 3.6, 95% CI 1.0–12.7).20 modest increase in risk of lung cancer associated It is possible that house dust in these areas acts as a with cadmium exposure. However, the high level of persistent source of cadmium exposure.20 variability in studies makes it difficult to measure the overall risk of developing lung cancer due to cadmium Effect of smoking exposure. There is no clear trend between duration of cadmium exposure and risk of lung cancer; however, It is not clear whether smoking interacts with cadmium one study suggests that the relative risk is up to 2.7 exposure to affect the risk of lung cancer—some studies for people exposed to higher levels of cadmium over show that risk from cadmium exposure increases with time (more than 2920 mg/m3-days, a measure of smoking;20 others show that the risk from cadmium cumulative cadmium exposure over time).89 exposure is higher for non-smokers.36,90 More studies are needed to determine the interaction between cadmium exposure and smoking as a risk of lung cancer.
Risk factors for lung cancer | An overview of the evidence 13 Asbestos
Asbestos is a naturally occurring mineral. There are six What is the risk? types of asbestos, characterised by the shape of their fibres: the long, narrow chrysotile (white asbestos); Research in this overview offers clear indication of an the shorter and wider amphibole types—amosite increased risk of lung cancer following exposure to and actinolite (brown asbestos); anthophylite and asbestos. Most studies of exposure to asbestos have crocidolite (blue asbestos); and tremolite.22 been undertaken on male populations, most likely because, historically, men have worked more often The health risks of asbestos have been well studied, than women in occupations such as mining and other and there is a substantial body of research on this industries that may be exposed to asbestos. topic, primarily relating to occupational asbestos exposure. IARC has identified that there is sufficient evidence to indicate that asbestos is a cause of lung Occupational exposure to asbestos cancer.22 As well as lung cancer, IARC has identified There is evidence to suggest that occupational that asbestos causes mesothelioma and cancer of the exposure to asbestos increases the risk of developing larynx and ovary.22 For the purposes of this evidence lung cancer by approximately 1.3–2.0 times.3 Studies overview, mesothelioma is not classified as lung have investigated occupations such as asbestos cancer, and studies on mesothelioma are therefore mining, various types of manufacturing, ship building, not included. railway construction and plumbing.
In the manufacturing industry, workers exposed to Exposure to asbestos asbestos generally have a higher risk of developing Asbestos was commonly used in building materials lung cancer. However, results were variable because in the form of asbestos cement, vinyl floor coverings, of the different ways in which exposure was lagging of pipes and boilers, and insulation. It was measured. A meta-analysis of several studies found used extensively in Australia, particularly between that manufacturing workers exposed to asbestos are 1945 and 1980, and was also mined in Australia.91 twice as likely to develop lung cancer than workers Asbestos was banned from use in building products who have not been exposed (relative risk 2.0, 95% CI 3,22 in Australia in 1989, although it remained in gaskets 1.7–2.4). Manufacturing workers at increased risk and brake linings until recently. It was completely include insulation workers (relative risk 2.8, 95% CI 92 3 prohibited in 2004 and cannot be imported, used 2.0–3.9), textile workers (2.2, 95% CI 1.8–2.6) and 3 or recycled.91 However, it is still present in buildings cement workers (1.8, 95% CI 1.4–2.4). Workers that were constructed using these materials before exposed to asbestos in other sectors of manufacturing, the ban. including rail workers, shipyard workers and plumbers, also show a significantly elevated risk of lung cancer The risk from asbestos is due to the inhalation of and are approximately 1.3 times more likely to develop fibres, especially in high doses or over long periods of lung cancer than those who have not been exposed time. This can occur as part of a person’s occupation (relative risk 1.3, 95% CI 1.1–1.6).3,22 However, results (e.g. asbestos miners, manufacturers of asbestos from studies on these workers were variable because building products, builders), or in other circumstances of differences in duration, intensity and type of such as home renovations, where drilling or other exposure. activities can release fibres into the air (which can be inhaled) or into a water supply (where they can be Overall, a person’s risk of developing lung cancer starts ingested in drinking water). to increase significantly after approximately 10 years of occupational exposure to asbestos, and this risk increases with increasing duration of exposure.3,22 The length of time between exposure to asbestos and development of lung cancer is usually 20–40 years.93
14 Risk factors for lung cancer | An overview of the evidence Non-occupational exposure to asbestos Type of asbestos fibre Results from the three studies on non-occupational It is not clear whether the type of asbestos fibre exposure to asbestos are variable. Two studies affects the risk of developing lung cancer. Many examined people living near asbestos industries: one studies include people who have been exposed to showed that risk increased with increasing exposure; multiple types of asbestos, particularly chrysotile the other showed no increase in risk.22 A study of and crocidolite, but detailed and accurate exposure residential exposure from asbestos-containing characteristics are often unavailable. This makes it whitewash found that risk increased with more than difficult to ascertain any differences in the risk of 20 years of exposure.94 More studies are required on lung cancer, between different types of asbestos non-occupational exposure to asbestos to clarify fibres. There is evidence, however, that chrysotile and the risks. crocidolite miners are at increased risk of developing lung cancer, with a relative risk of between 1.1 and Asbestosis and lung cancer 1.7.3,95 This evidence suggests that both chrysotile and amphibole fibre types increase the risk of lung cancer. Some research has focused on whether asbestosis Recent studies suggest that lung cancer may take (a disease in which the lungs become inflamed and longer to develop after exposure to chrysotile asbestos scarred as a result of exposure to asbestos) is related than after exposure to amphibole types of asbestos.96,97 to the development of lung cancer. Studies show that the risk of lung cancer in people with asbestosis is higher than in the general population (standardised mortality ratio ranged from 1.7 to 6.2 across different studies),22 and also higher than in people who have been exposed to asbestos but do not have asbestosis.23 However, the evidence also suggests that asbestosis is not necessary for asbestos exposure to present a significant risk of lung cancer.
Effect of smoking There is evidence from all included studies in the systematic review that smoking (or a history of smoking) compounds the risk of lung cancer in people already at increased risk due to their high exposure to asbestos, and that the relationship between asbestos and smoking in lung cancer is more than additive. One large study from the United Kingdom showed that people who smoked one pack of cigarettes per day for 35 years and had been exposed to asbestos in their jobs for more than 30 years were 26 times more likely to develop lung cancer than people who had never smoked and had been exposed to only low levels of asbestos in their jobs (relative risk 26.2, 95% CI 13.0–53.1).21 The risk was lower for former smokers, but remained highly significant; former smokers (one pack per day for 17 years) exposed to asbestos for more than 30 years were almost 10 times more likely to develop lung cancer than people who had never smoked or been exposed to significant levels of asbestos (relative risk 9.7, 95% CI 4.7–20.0).21 In the same study, never-smokers exposed to asbestos for more than 30 years had a relative risk of developing lung cancer of 1.6 (95% CI 0.6–4.2).21
Risk factors for lung cancer | An overview of the evidence 15 Designer: Change “Exposure in silicosis sufferers” to “Exposure in people with silicosis”
Silica
Silica is a term used to describe a group of minerals Studies suggest that the risk of developing lung that contain silicon and oxygen. These minerals cancer is affected by the duration of silica exposure. are common in nature, and silica is found in almost One study found that the risk of lung cancer did not all types of rock, clay, gravel and sand, as well as in increase to a statistically significant extent until people construction materials such as concrete, bricks and tiles. had been exposed to silica for 26–51 years, leading to Silica exists in two forms: crystalline and amorphous. a relative risk of 1.7 (95% CI 1.1–2.4).26
Inhaled crystalline silica resulting from occupational The intensity of exposure (how much silica a person exposure has been identified by IARC to increase the risk is exposed to) also increases the risk—people with a of lung cancer.98 Its ability to cause cancer depends on cumulative exposure of 1 mg/m3/year have a relative the characteristics of the silica, and on other factors that risk of 1.2, and this increases to 1.8 with a cumulative might affect the way it interacts with a person’s body.98 exposure of 6 mg/m3/year.27 Exposure to silica Risk of lung cancer in people with silicosis Silicosis is a disease that causes scarring of the lungs. It Crystalline silica can form dust particles that are small is caused by repeated and prolonged exposure to silica. enough to be inhaled. Exposure to silica can occur in a People with silicosis are approximately twice as likely person’s occupation, particularly in industries such as to develop lung cancer as people who are exposed to founding, pottery, sandblasting, construction, quarrying, silica but do not have silicosis (relative risk 2.0).3,32,33,36-38 and clay and glass manufacturing and processing. Effect of smoking What is the risk? People who smoke and are exposed to silica have a The relative risk of developing lung cancer in higher risk of developing lung cancer than non-smokers people exposed to silica is similar across a range of who are exposed to silica. This risk increases the more a occupations. Studies show that people exposed to person smokes, and the more silica they are exposed to. silica in mining, quarrying, and the granite, ceramic Results from an analysis of two Canadian studies and steel industries are approximately 1.2–1.3 times examining the joint effects of silica exposure and more likely to develop lung cancer than people who smoking showed that all categories of smoker are are not exposed.3,24,25 associated with increased risk of lung cancer. For any Combined data from people exposed to silica in the level of silica exposure, the relative risk of developing mining industry (lead, zinc, gold and copper) show lung cancer is 3.2 (95% CI 1.5–6.8) for people who they have a relative risk of developing lung cancer of have smoked one pack of cigarettes per day for approximately 1.2 (95% CI 1.0–1.4), although different less than 20 years.31 The relative risk increases to studies collected data in different ways, and study 6.8 (95% CI 4.0–11.4) for people who have smoked participants were exposed to varying levels of silica one pack of cigarettes per day for 20–50 years, and in different types of mines.3 up to 23.2 (95% CI 14.4–37.4) for people who have smoked one pack of cigarettes per day for more than Increased risk of lung cancer is also shown for 50 years.31 In the same study, the relative risk of lung industrial workers in ceramics (relative risk 1.2, 95% CI cancer due to silica exposure in non-smokers was 1.3 1.1–1.4) and diatomaceous earth industry (relative risk (95% CI 0.5–3.2).31 The relative risks for both smokers 1.4, 95% CI 1.1–1.9).3 and non-smokers were higher for ‘substantial’ silica exposure (although this level of exposure was not well defined).31 16 Risk factors for lung cancer | An overview of the evidence Iron and steel founding
Founding is the process of pouring molten metal or There is insufficient evidence to determine how each glass into a mould to create a new shape or object. of the individual risk factors associated with foundries Iron and steel foundries make parts for machinery, contributes to the overall risk of lung cancer; however, motor vehicles, railway engines, stoves and wheels. one study found that foundry workers exposed to Workers in this occupation may be exposed to several silica had a significantly higher risk of lung cancer.100 risk factors for lung cancer, such as asbestos, polycyclic aromatic hydrocarbons, silica, chromium, nickel The longer a person is exposed to iron or steel and cadmium.32 founding, the higher their risk of lung cancer. An analysis of studies showed that people who had IARC has identified that there is sufficient evidence to worked in the industry for less than 10 years did not indicate that occupational exposures during iron and have a higher risk of developing lung cancer, but steel founding are a cause of lung cancer.99 people who had worked in iron and steel founding for more than 30 years were 1.9 times more likely to develop lung cancer than people who do not work in Exposure to iron and steel founding the industry (relative risk 1.9, 95% CI 1.1–3.1).3 People who work in the production processes of iron and steel founding can be exposed to several risk Effect of smoking factors for lung cancer.32 People who work in office or administrative roles at foundries are unlikely to be Studies of iron and steel founding and smoking exposed and are not at increased risk of developing indicate that foundry workers who smoke are at lung cancer.32 higher risk of developing lung cancer than foundry workers who do not smoke, and the risk increases with increased smoking.33-35 However, the extent of What is the risk? risk varies significantly among studies: for the highest 35 Overall, evidence suggests that iron and steel foundry category of smoking, relative risks ranged from 2.8 33 workers are 1.3–1.4 times more likely to develop lung to 118.1. The studies also measured the amount of cancer than people who do not work at foundries.3,18 smoking in different ways, preventing meta-analysis of Two studies examined the risks associated with the results. different jobs within a foundry. Results of these studies showed that those workers at the industrial site engaged in production showed an increased risk of lung cancer compared with the general population, while office workers at the industrial site did not. Exploring particular roles, one study showed that only blast furnace workers had a significantly higher risk of lung cancer (odds ratio 2.6, 95% CI 1.3–5.2), and no significant elevation in risk was found for workers in coke batteries, steel mills, lamination facilities, steel foundries, maintenance furnaces or facilities producing coke byproducts.32,33 Further research on these individual studies is required to align risk of lung cancer with specific roles in the industry with any certainty.
Risk factors for lung cancer | An overview of the evidence 17 Nickel
Nickel and its compounds are naturally present in What is the risk? the Earth’s crust. They can be released into the air by natural processes such as windblown dust, volcanic Evidence suggests that occupational exposure to eruptions and bushfires, or through human activities nickel represents a significant, but modest, increase such as mining, smelting, refining, manufacturing, in the risk of lung cancer.3 The variability in studies burning fossil fuels and burning waste.101 Nickel is included in the systematic review makes it difficult often combined with other metals to form alloys that to provide a clear, quantifiable risk. However, the are used in stainless steel, electroplating, coinage, studies are consistent in the risk they demonstrate. The catalysts and welding components. Nickel can majority of research informing the systematic review accumulate in the lungs, interfering with cells of was conducted in Europe, with no included studies the immune system and damaging DNA, which can conducted in Australia. contribute to cancer.101 Two pooled analyses show that people who are IARC has identified that there is sufficient evidence exposed to nickel in their jobs are approximately that nickel compounds and nickel metal are a 1.3 times more likely to develop lung cancer than cause of lung cancer. Nickel compounds and nickel people who are not exposed to nickel.3,36,103 A study in metal also cause cancers of the nasal cavity and Norway showed that work in a nickel refinery for more paranasal sinuses.101 than one year significantly increased the risk of lung cancer for smelter workers (odds ratio 2.7, 95% CI 2.1–3.6), roasters (odds ratio 3.4, 95% CI 2.3–4.8) and Exposure to nickel nickel electrolysis workers (odds ratio 4.0, 95% CI Nickel can be inhaled, ingested through food or 3.3–4.8) compared with other Norwegian men.37 drinking water, or absorbed through the skin. Most The risk of developing lung cancer due to nickel people are exposed to nickel in the air and in food, exposure appears to increase with increasing duration but this level of exposure is not considered to be a of exposure. Evidence from a pooled analysis of two risk. People who work with nickel in their jobs can be studies in a Canadian nickel refinery found that the risk exposed to higher levels of nickel through fumes, dust of lung cancer was only significant for workers who and mist.101,102 had been exposed to nickel for more than 20 years All the included studies investigated occupational (relative risk 1.6, 95% CI 1.1–2.3).36,104 exposure of male workers to various forms of nickel. The amount of nickel exposure over time also appears to affect the risk of developing lung cancer. In particular, exposure to high levels of water-soluble nickel was found in two studies to increase the relative risk to approximately 3.1 (95% CI 1.7–5.5) compared with people who are not exposed to nickel.105 The two studies that measured cumulative exposure used different amounts for the highest exposure category, but the trend of increased risk was the same in both studies.105,106
18 Risk factors for lung cancer | An overview of the evidence Type of nickel compound One study examining the type of nickel compound and lung cancer risk found that exposure to water- soluble nickel, nickel oxide, nickel sulfide and metallic nickel all increased the risk of lung cancer, compared with the general population of men in Norway.105 At low exposure (cumulative exposures of 0.01–0.05 mg/m3 over time, depending on the compound), risks (odds ratios) ranged from 1.3 to 1.7. Nickel sulfide became a significant risk at lower concentrations than other compounds, and water- soluble nickel had the highest risk at the highest concentrations.105
Effect of smoking Smokers who are exposed to nickel appear to have a higher risk of developing lung cancer than non- smokers who are exposed to nickel, and this risk increases with increasing nickel exposure. In one study, nickel refinery workers exposed to less than 1 g/m3 of nickel per year who have ever smoked were 5.6 times more likely to develop lung cancer than non-smoking nickel refinery workers (relative risk 5.6, 95% CI 2.0– 15.0).37 Workers exposed to more than 1 g/m3 of nickel per year who have ever smoked were approximately 9 times more likely to develop lung cancer than workers who had never smoked (relative risk 9.1, 95% CI 3.4–25.0).37 However, there was considerable variability in the results of studies examining the effect of smoking in people exposed to nickel.
Risk factors for lung cancer | An overview of the evidence 19 Beryllium
Beryllium is a naturally occurring metal that is found What is the risk? in rocks, coal, oil, volcanic dust and soil.107 It is mostly used in the nuclear and aerospace industries to Evidence suggests that occupational exposure to make precision instruments and structures, as well as beryllium represents a modest risk factor for lung high-speed computers and audio components.107,108 cancer, and any risk is dependent on a relatively In Australia, beryllium is mainly used in small high level of exposure. All the studies on beryllium quantities in electronic components.42 It can also be exposure included in the systematic review have been part of emissions from fossil fuels, such as coal-fired of men who worked in beryllium processing plants in power stations.42 the United States for at least two days between 1940 and 1970. The generalisability of results outside this IARC has identified that there is sufficient evidence to cohort is uncertain. indicate that beryllium and its compounds are a cause of lung cancer.109 However, not all forms of beryllium Overall, the relative risk of developing lung cancer in are thought to be equally toxic, and further research these men is 1.0–1.2, but this varied among processing is required to fully understand the health effects of plants. In the plants with high levels of exposure, the beryllium exposure.42 relative risk was approximately 1.4–1.5 compared with non-exposed workers.38-41 It is unlikely that, in Australia today, workers would be exposed to beryllium at levels Exposure to beryllium that may present an increased risk of lung cancer. Beryllium can be inhaled or ingested. Ingesting The type of beryllium may also affect the risk of beryllium is not associated with harmful effects developing lung cancer. The results of one small study because very little of it is absorbed through the suggest that exposure to different types of beryllium gastrointestinal tract, but inhaling beryllium can irritate may present different levels of lung cancer risk.41 the eyes, skin and respiratory tract, and inflame the However, the evidence in this regard, being from one lungs. Inhaling beryllium can cause acute beryllium small study, is too scant to draw any firm conclusion disease, which has symptoms similar to pneumonia on lung cancer risks. and can be fatal.42,109 The studies included in the systematic review indicate Exposure to beryllium can be an occupational risk that only at relatively high occupational exposures in some specialised workplaces such as mining is there an elevated risk of lung cancer associated and processing beryllium ores, manufacturing with beryllium exposure. Results from the US studies and processing beryllium alloys or compounds, suggest that low exposure, even at levels equivalent or working with metals that contain beryllium.42 to average exposure in industry, does not represent a However, relatively high levels of beryllium exposure significant risk of lung cancer.3 are required to increase risk of lung cancer.42 In Australia today, it is unlikely that workers or people No evidence was identified that demonstrated an in their domestic environments would be exposed effect of smoking on the risk of lung cancer in people to beryllium at levels that may increase the risk of exposed to beryllium. lung cancer.42
20 Risk factors for lung cancer | An overview of the evidence Painting as an occupation
More than 41 000 people are employed as painters There was inconsistency in the evidence regarding the in Australia.110 These workers use paints, varnishes impact of duration of employment as a painter or a and stains to protect or change the appearance spray painter on lung cancer risk. of buildings and structures. Paint contains a range of pigments, binders, solvents and other additives, No evidence was identified that demonstrated an which differ depending on the desired properties of effect of smoking on the risk of lung cancer in painters. the paint.
IARC has identified that there is sufficient evidence to indicate that occupational exposure as a painter is a cause of lung cancer.111 IARC has also identified that there is sufficient evidence to indicate that occupational exposure as a painter is a cause of mesothelioma and cancer of the bladder.111 Spray painting is thought to be more hazardous than non-spray painting because the paint is sprayed into fine particles that can be inhaled easily.43 Workers in the painting trade may also be exposed to other risk factors for lung cancer, such as asbestos, chromium and cadmium.44,111
Exposure to paint People who work with paint every day in their occupation have much higher exposure than people who do not work as painters. Most studies on painting as an occupation used a person’s job title or classification as the measure of exposure, rather than actual exposure to particular paints, environments or other factors; this makes it difficult to determine the precise aspects of painting as an occupation that can increase risk.
What is the risk? The research identified and synthesised in the systematic review suggests that occupational exposure to paint represents a modest risk factor for lung cancer. The combined results of several studies show that, overall, people who work as painters are 1.3 times more likely to develop lung cancer than people who do not work as painters.43-46 One study found that painters in the construction industry have a risk (odds ratio) of 1.6 (95% CI 1.0–3.1) compared with non- painters. This may be due to their exposure to other risk factors such as asbestos or silica.46
Risk factors for lung cancer | An overview of the evidence 21 Chromium VI
Chromium is a natural chemical that occurs in manufacturing workers found that people who had two forms—chromium III, which is non-toxic, and been exposed to chromium VI for up to 10 years chromium VI.112 Chromium compounds are used had a relative risk of lung cancer of 1.2 (95% CI 1.1– in bricks, linings for furnaces, chrome plating, dye 1.4);117 another study found that people exposed to manufacture, wood and water treatment, galvanising, chromium dust for more than 20 years had a relative printing, paints, degreasers and rust converters. risk of 1.5 (1.0–2.3)19 compared with unexposed Chromium can be breathed in or ingested through workers. However, three other studies showed no contaminated food or water, where it is absorbed into significant increase in risk, even after adjusting for the the body. Once inside the body’s cells, chromium VI amount of exposure over time.36,48,118 breaks down, forming reactive chemicals that can damage DNA and contribute to cancer. The amount of chromium exposure may have a greater effect on risk than the length of time a IARC has identified that there is sufficient evidence to person is exposed. One study measured the amount indicate that chromium VI compounds are a cause of of chromium in people’s urine to determine their lung cancer.112 occupational chromium exposure. People with less than 200 grams per litre-years (g/L-year, a measure of the concentration of chromium in urine multiplied Exposure to chromium VI by the number of years of exposure) did not have Exposure to chromium VI can occur in occupations an increased risk of lung cancer, even 20 years after that involve the production, use and welding of they had been exposed to chromium. However, chromium-containing alloys (such as stainless steel people with urinary chromium levels of more than and high-chromium steel); the production and use of 200 g/L-year had a twofold greater risk of lung cancer, chromium-containing paints (such as in the aerospace, regardless of how much time had passed since they construction and maritime industries); electroplating; were exposed.48 catalysts; chromic acid and pesticides.112 People who are exposed to chromium VI may also be exposed to No evidence was identified that demonstrated the other risk factors for lung cancer in their workplaces, effect of smoking on the risk of lung cancer in people and this makes the risk due to chromium difficult exposed to chromium VI. to measure.113,114 Chromium VI is also present in tobacco smoke.115,116
What is the risk? Exposure to chromium VI may increase the risk of lung cancer. Combined results of many studies indicate that people who are exposed to chromium VI are at approximately 1.2 times greater risk of lung cancer than people who are not exposed (standardised mortality ratio 1.2, 95% CI 1.1–1.3).47 Other studies show mixed results, although the trend shows a likely increased risk of lung cancer.112 However, the risk estimates for many studies are not precise, and relevant details about the people involved in the studies are lacking.
There is insufficient evidence to determine whether duration of exposure to chromium VI affects the risk of developing lung cancer. A study in aircraft
22 Risk factors for lung cancer | An overview of the evidence Air pollution
This section of the overview focuses on air pollution Sulfur dioxide and nitrogen dioxide, which are gaseous in the outside air, including gases and particles that components of air pollution, do not appear to increase comprise urban pollution, and pollution from vehicle the risk of lung cancer.49,51 However, there is mixed exhaust. It does not include indoor air pollution. evidence as to whether other nitrogen oxides are Air pollution can include chemicals such as sulfur associated with a small increase in risk of lung cancer dioxide, nitrogen dioxide and nitrogen oxides, and a (relative risk 1.1, 95% CI 1.0–1.2).49,52 range of particles known as particulate matter (PM). PM is classified according to the size of the particles: None of the included studies reported an increase inhalable (particles 10 micrometres [μm] or less in in lung cancer risk as a result of living near busy or major roads.49,51,52 diameter, also known as PM10), fine (particles 2.5 μm or less in diameter; PM2.5) and ultrafine (particles 0.1 μm Limited evidence was available on the effect of or less in diameter; PM0.1). smoking on the risk of lung cancer related to air pollution. Results from a single study reported no Exposure to air pollution increased risk of lung cancer as a result of smoking in people exposed to air pollution.51 The level of air pollution in Australia compares favourably with many other countries: the average
PM2.5 level over six years is 12 micrograms (μg) of particles per cubic metre of air (μg/m3).119 The global Diesel exhaust as a risk factor for lung cancer average is 27 μg/m3, and some areas report more than 100 μg/m3.119 As very high levels of pollution are not In June 2012, the International Agency for comparable to conditions in Australia, studies in these Research on Cancer (IARC) identified that areas (e.g. China) were not included in the systematic there is sufficient evidence that exposure to review.3 diesel engine exhaust is associated with an increased risk of lung cancer.54 While large People living in urban and industrial areas may be populations are exposed to diesel exhaust exposed to more air pollution than those living in in everyday life, whether as part of their rural areas. occupation or through exposure to motor vehicle and other diesel engine exhausts in What is the risk? the ambient air, the main studies that led to There is evidence that exposure to fine particulate IARC’s conclusion were in highly exposed workers. Exposure to diesel exhaust is not matter (PM2.5) in air pollution increases the risk of lung cancer. Studies in the United States and Europe have included as a risk factor in this overview, as estimated relative risks of lung cancer for people who the systematic review was conducted before are exposed to fine particulate matter (PM2.5) in air IARC’s classification of diesel engine exhaust pollution of 1.2–1.3 compared with people who are as a substance with sufficient evidence to be 49,50 not exposed to similar levels of PM2.5. For example, causally associated with lung cancer. 3 people who are exposed to 10 μg/m of PM2.5 for one year are 1.2 times more likely to develop lung cancer than people who have not been exposed to such levels of pollution (relative risk 1.2, 95% CI 1.1–1.3).49 The risk of developing lung cancer from cumulative exposure to fine particulate matter does not appear to increase over time—one study reported that the relative risk after 21 years’ exposure is not significantly different from the risk after one year’s exposure.50
Risk factors for lung cancer | An overview of the evidence 23 Family history
A person’s family history can be useful in assessing The role(s) of modifiable factors (such as shared their risk of developing cancer. Some types of environment) and non-modifiable factors (such as cancer are linked to particular genes, so if one family genes) in the association between family history and member—particularly a first-degree relative, such as increased risk of lung cancer is unclear. Research into a parent or sibling—has that type of cancer, it may non-modifiable risk factors is now moving towards indicate that other members of the family are at studies of genomics, where genetic variations that increased risk. predispose to lung cancer are being identified, described and quantified. Lung cancer is usually associated with environmental rather than genetic triggers. However, because families share environmental and behavioural characteristics as well as genetic traits, knowledge of a person’s family history of lung cancer can help to increase understanding of shared risks. Although research is increasing on genetic factors associated with lung cancer, such as particular enzymes or protein profiles, the systematic review on which this overview is based investigated studies on family relationships only.
Family history can include both modifiable (environmental, behavioural) and non-modifiable (genetic) risk factors.
What is the risk? There is evidence to suggest that a person who has a family member with lung cancer is approximately twice as likely to develop lung cancer as someone without a family history of the disease (relative risk 2.0).3 The risk appears to be most significant if two or more family members had lung cancer (odds ratio 3.6, 95% CI 1.6–8.3), or if a person’s mother had lung cancer (odds ratio 2.2, 95% CI 1.3–4.0).53
People with a family history of lung cancer are more likely to smoke than people without a family history.53 Smokers who had a family member with lung cancer were at increased risk relative to those who did not smoke.
24 Risk factors for lung cancer | An overview of the evidence Factors with limited evidence of an association with lung cancer
Consumption of red meat Processed meat Consumption of large amounts of processed meat also and processed meat appeared to increase risk of lung cancer by a similar small amount. A meta-analysis of nine studies suggests Red meat (such as beef and lamb) and processed that people who eat large amounts of processed meat meat (such as cured meats, sausage, ham and are approximately 1.2 times more likely to develop bacon) contain salt, saturated fats and some lung cancer than people who eat little or no processed compounds that may contribute to cancer.120 Grilling meat (relative risk 1.2, 95% CI 1.0–1.3).3 However, this or barbecuing red meat can also release polycyclic conclusion should be interpreted with caution, as aromatic hydrocarbons,121 which are a risk factor for studies varied in their definitions of ‘processed meat’ lung cancer.80,81 and in their categories of consumption (the lowest category was no serves of processed meat or less than Australians consume approximately 87.4 kilograms (kg) 10 g per day; the highest category varied but was of red meat per person per year, or 239 grams (g) per less than for red meat consumption). The method of person per day.122 However, some people eat no red processing (e.g. salting, smoking) and whether the meat, and others may eat more than this amount. meat was raw or cooked also varied across studies. Studies of red meat and The effect of duration of exposure to large amounts of processed meat on the risk of developing lung cancer processed meat is not clear. Red meat The effect of smoking on the risk of developing lung cancer from red meat or processed meat consumption Evidence suggests that people who eat large amounts is unclear. Two studies suggested that smoking of red meat may be at increased risk of developing increased the risk of lung cancer in men and women lung cancer compared with people who eat little who ate large amounts of red meat.124,125 However, 3 or no red meat (relative risk 1.1, 95% CI 1.1–1.2). the wide confidence intervals (especially for women) However, this conclusion should be interpreted with make it difficult to determine the exact increase in risk. caution, as studies varied in the way they measured A single study in men who ate more than 4.6 serves of lung cancer risk in people who ate large quantities of processed meat per week found that former smokers, red meat and in the way that red meat consumption but not current smokers, were almost twice as likely was categorised—the lowest exposure category was to develop lung cancer due to high processed meat usually people who ate no red meat or less than 10 g consumption as men who ate little or no processed per day, while the highest category ranged from more meat (odds ratio 1.9, 95% CI 1.1–3.1).125 However, more 123 than 80 g per day to more than nine serves per studies are required to further investigate this risk. week.124 Overall, this result is based on approximately 5–10 portions per week; however, portion size across studies was variable. None of the studies investigated whether the method of cooking the meat affected risk.
The effect of duration of exposure to large amounts of red meat on the risk of developing lung cancer is not clear. Most studies used questionnaires to evaluate people’s meat intake; some of these asked people about their usual diet over the past 2–5 years, but others did not account for duration of exposure.
Risk factors for lung cancer | An overview of the evidence 25 Alcohol consumption Dietary and blood Approximately 8.9% of Australians over the age of cholesterol 14 years drink alcohol on a daily basis.126 Men consume more alcohol than women: 12% of men drink alcohol Cholesterol is important for healthy cell function, but daily, and 48% drink alcohol weekly, compared with excess cholesterol can be harmful. Cholesterol is found 6% and 35% of women, respectively.126 in many foods, and dietary cholesterol intake affects the amount of cholesterol that circulates in a person’s IARC has identified that there are inadequate data blood. It is estimated that every 100 g of cholesterol to indicate that alcohol consumption is a cause of consumed in a person’s diet raises their blood 127 lung cancer. However, IARC has identified that cholesterol by 2–3%.138 there is sufficient evidence to indicate that alcohol consumption causes cancers of the oral cavity, Different foods contain different levels of cholesterol; pharynx, larynx, oesophagus, colorectum, liver therefore, exposure depends on diet. Foods that are (hepatocellular carcinoma) and breast.128 high in fat, such as fast food, butter and eggs, are often associated with high levels of cholesterol, while fresh Studies of alcohol consumption fruit and vegetables contain little cholesterol. IARC has identified that the evidence is inadequate The studies examined in the systematic review suggest to indicate whether dietary cholesterol is a cause of that alcohol consumption does not independently lung cancer.139 increase the risk of lung cancer.3 However, studies varied in focus and measured alcohol consumption in different ways, and not all of them adjusted Studies of dietary and blood for smoking. cholesterol Some studies found an increased risk of lung cancer Studies included in the systematic review measured with high alcohol consumption (more than five drinks cholesterol intake in several different ways, but this 129,130 per day), but other studies found no significant was usually per day or per week, with no indication of association between any level of drinking and the length of time (e.g. number of years) a person had 131-134 lung cancer. been consuming that level of cholesterol in their diet.3 There are no clear data in the studies of lung cancer effects by duration of exposure to a particular level of Dietary cholesterol alcohol consumption. The length of follow-up in these While studies of dietary cholesterol and risk of lung studies ranged from 7 to 17 years. cancer have mixed results, overall the evidence Some studies suggest that smoking may interact suggests that dietary cholesterol intake does not with alcohol consumption to increase the risk of increase the risk of developing lung cancer. Some lung cancer.135-137 studies found no association between the amount of cholesterol in a person’s diet and their risk of lung cancer,140,141 while others found relative risks of up to approximately 1.6 for people with high- cholesterol diets.142,143
A large pooled analysis showed no interaction between smoking, dietary cholesterol and risk of lung cancer.141
Blood cholesterol High blood cholesterol does not appear to impart any risk of lung cancer on individuals. Rather, the evidence suggests that high blood cholesterol may have a modest protective effect and reduce the risk of lung cancer.
Conversely, if plasma cholesterol concentrations are low (<160 milligrams per decilitre), there is some evidence to suggest that the risk of lung cancer is increased.144–147 However, this does not suggest that low cholesterol is a risk factor for lung cancer—it is more plausible that this is a non-causal correlation.
26 Risk factors for lung cancer | An overview of the evidence Exposure to birds Exposure to wood dust The potential for pet birds to increase indoor air Wood dust can be present at high levels in industries pollution and spread disease has led to research into that work with forestry products, such as furniture their association with various diseases, including lung factories, pulp mills and paper mills, as well as in cancer. Pet birds can be kept either inside the house woodworking as a hobby. Manipulation of wood, such or outdoors in an aviary or similar enclosure. Exposure as drilling and sawing, can create fine dust particles to birds can also occur in a person’s occupation that can be inhaled. Exposure to wood dust usually (e.g. aviary worker, zookeeper) but no studies occurs as part of a person’s occupation. identified have investigated the risk of developing lung cancer from occupational exposure to birds. Studies of wood dust It is difficult to measure the duration and intensity of Studies of exposure to birds exposure to wood dust, and this makes it difficult to While studies on exposure to birds and risk of lung determine its effect on lung cancer risk. Also, people cancer have mixed results, combining the results of who are exposed to wood dust (particularly in the several studies suggests that exposure to birds does workplace) may also be exposed to other risk factors not increase the risk of lung cancer overall.3 for lung cancer, such as asbestos or other types of dust, which can confound results. Three of four studies found no association between the lengths of time that people were exposed to birds People who are exposed to wood dust are not likely and their risk of lung cancer.148-151 to have a higher risk of developing lung cancer than people who are not exposed. Four studies found no Studies suggest that smoking does not affect the risk association between wood dust exposure and lung 148,149 of lung cancer from exposure to birds. cancer,152-155 and two studies found small increases in risk.156,157 These small increases were found only after approximately 20 years of exposure to wood dust,156,157 suggesting that increased risk may be apparent for long duration of exposure.
Almost all the studies included men only, and none of the studies looked at the effect of smoking on risk of lung cancer after wood dust exposure.
Risk factors for lung cancer | An overview of the evidence 27 Physical activity Physical activity is associated with daily living, work and leisure activities, and is considered to be beneficial for health and the prevention of chronic diseases.
Studies of physical activity Increased physical activity is not associated with an increased risk of lung cancer but may rather reduce the risk of the disease.
A research synthesis and six research studies have been included in the systematic review to investigate the association between physical activity and risk of lung cancer, with most, but not all, suggesting an inverse association between higher levels of physical activity and lung cancer risk.3,55 The findings presented in each study included in the systematic review varied in terms of type, frequency and duration of physical activity, amount of energy expended and intensity of physical activity, precluding an overall assessment of risk reduction. In addition, limitations of these studies included the influence of factors outside the control of the investigators, such as subjective interpretation of questionnaires.
Most studies, however, suggest that people who participate in some physical activity may be at a reduced risk of developing lung cancer when compared to those who are physically inactive.3,55,56
Refer to the National Physical Activity Guidelines for current Australian recommendations for physical activity.158
28 Risk factors for lung cancer | An overview of the evidence Glossary
Absolute risk A person’s chance of developing a disease over a particular period of time. It is calculated by dividing the number of people who have the disease in a particular group by the total number of people in that group. Active smoking Smoking tobacco through any means, including cigarettes, cigars, pipes, bidis and waterpipes. It does not include exposure to other people’s tobacco smoke (see Passive smoking). Becquerel The SI unit of radioactivity. Confidence interval (CI) A measure of the precision of the risk estimate—the narrower the interval, the more precise the estimate of the risk, and the less likely that the risk would be subject to chance variation. A 95% CI indicates that we are 95% certain that the true value of the estimate lies within that range. Incidence The number of new cases of an illness that occur during a given period in a specified population. Level of evidence An indication of the quality of the evidence, based on the likelihood of the study results being affected by bias. In this overview, levels of evidence range from Level I (high quality, low level of bias) to Level IV (lower quality, higher likelihood of bias). Lung cancer Uncontrolled growth of cells in the lung. Different types of lung cancer originate in different types of lung cells, and include small cell carcinoma, non–small cell carcinoma and other types. Cancers that originate in other parts of the body can spread to the lungs and cause secondary cancers; however, this overview only considers primary lung cancer. Mesothelioma Cancer of the lining of the chest and abdominal cavities. Pleural mesothelioma is a type of cancer affecting the membrane (the pleura) that covers and protects the lungs. Mesothelioma is not a primary lung cancer, so is not included in this overview. Odds ratio A measure of the association between an exposure and an outcome. It describes the odds that an outcome (e.g. lung cancer) will occur after exposure (to a certain risk factor), compared with the odds of the outcome occurring without the exposure. In rare diseases such as lung cancer, odds ratios can be interpreted as equivalent to relative risks. Passive smoking When tobacco smoke (including the smoke released from a burning tobacco product and the exhaled smoke from the person smoking) is inhaled by a person other than through active smoking (i.e. exposure to other people’s tobacco smoke). Also known as involuntary smoking, exposure to environmental tobacco smoke or second-hand smoke, and tobacco smoke pollution. Primary cancer A tumour that is at the site where it first formed (see also Secondary cancer). Relative risk A person’s chance of developing a disease over a particular period of time relative to another person’s chance of developing the disease. It is calculated by dividing the absolute risk of a group of people who are exposed to a risk factor by the absolute risk of a group of people who are not exposed to the risk factor. Relative risk indicates how many times more likely a person in the exposed group is to develop the disease. Risk factor Any factor that is associated with a greater risk of a health disorder or other unwanted condition or event. Some risk factors are regarded as causes of disease; others are not causative. Some risk factors can be modified; others cannot. Secondary cancer A tumour that originated from a cancer elsewhere in the body.
Risk factors for lung cancer | An overview of the evidence 29 Standardised mortality ratio The ratio of deaths in the study population to those in the reference population, adjusted for age. For example, a standardised mortality ratio of 1.5 indicates that there were 50% more deaths in the study population. Statistical significance An indication from a statistical test that an observed difference or association may be significant or ‘real’ because it is unlikely to be due just to chance. A statistical result is usually said to be significant if it would occur by chance only once in 20 times or less often. Systematic review An assessment of published studies that uses rigorous, standardised methods for searching for, selecting, critically appraising and synthesising articles to answer a defined research question. This minimises bias and provides a high level of evidence. See also Level of evidence.
30 Risk factors for lung cancer | An overview of the evidence Appendix 1 International Agency for Research on Cancer (IARC)
The IARC monographs1 identify factors that can The IARC Working Group also considers the body increase the risk of human cancer. Interdisciplinary of evidence as a whole, in order to reach an overall working groups of expert scientists review the evaluation of the carcinogenicity of the agent to published studies and evaluate the weight of the humans. The categorisation of an agent into one of the evidence that an agent can increase risk of cancer. following four groups is a matter of scientific judgment Agents are then categorised as carcinogenic, probably that reflects the strength of the evidence derived from or possibly carcinogenic, or not carcinogenic to studies in humans and experimental animals, and from humans, based on the strength of the evidence. mechanistic and other relevant data: Group 1 carcinogen: The agent is carcinogenic The evidence relevant to carcinogenicity of agents to humans. This category is used when there is from studies in humans is classified into four sufficient evidence of carcinogenicity in humans. categories by the IARC Working Group: Group 2: Group 2A (probably carcinogenic to Sufficient evidence of carcinogenicity (highest IARC classification for carcinogenicity): The humans) or Group 2B (possibly carcinogenic Working Group considers that a causal relationship to humans). This category includes agents for has been established between exposure to which, at one extreme, the degree of evidence of the agent and human cancer. That is, a positive carcinogenicity in humans is almost sufficient, as relationship has been observed between the well as those for which, at the other extreme, there exposure and cancer in studies in which chance, are no human data but for which there is evidence bias and confounding could be ruled out with of carcinogenicity in experimental animals. reasonable confidence. Group 3: The agent is not classifiable as to its carcinogenicity to humans. This category is used Limited evidence of carcinogenicity (positive association): A positive association has been most commonly for agents for which the evidence observed between exposure to the agent of carcinogenicity is inadequate in humans and and cancer for which a causal interpretation is inadequate or limited in experimental animals. considered by the Working Group to be credible, Group 4: The agent is probably not but chance, bias or confounding could not be carcinogenic to humans. This category is used ruled out with reasonable confidence. for agents for which there is evidence suggesting lack of carcinogenicity in humans and in Inadequate evidence of carcinogenicity: The available studies are of insufficient quality, experimental animals. consistency or statistical power to permit a conclusion regarding the presence or absence of a causal association between exposure and cancer, or no data on cancer in humans are available.
Evidence suggesting lack of carcinogenicity: There are several adequate studies covering the full range of levels of exposure that humans are known to encounter, which are mutually consistent in not showing a positive association between exposure to the agent and any studied cancer at any observed level of exposure.
1 http://monographs.iarc.fr/index.php
Risk factors for lung cancer | An overview of the evidence 31 References
1 Australian Institute of Health and Welfare, since exposure and age at exposure. Radiat Cancer Australia. Lung cancer in Australia: Res 2008;169(2):125–37. an overview. Cat. no. CAN 58. Canberra: Australian Institute of Health and Welfare, 11 Schnelzer M, Hammer GP, Kreuzer M, 2011. Tschense A, Grosche B. Accounting for smoking in the radon-related lung cancer 2 Australian Institute of Health and Welfare, risk among German uranium miners: results Australasian Association of Cancer Registries. of a nested case–control study. Health Phys Cancer in Australia: an overview, 2010. Cancer 2010;98(1):20–8. series no. 60. Cat. no. CAN 56. Canberra: Australian Institute of Health and Welfare, 12 Leuraud K, Schnelzer M, Tomasek L, Hunter N, 2010. Timarche M, Grosche B et al. Radon, smoking and lung cancer risk: results of a joint 3 Joanna Briggs Institute. Risk factors for lung analysis of three European case–control cancer: a systematic review. Report prepared studies among uranium miners. Radiat Res for Cancer Australia. Adelaide: Joanna Briggs 2011;176(3):375–87. Institute, 2012. 13 Pavia M, Bianco A, Pileggi C, Angelillo IF. Meta- 4 International Agency for Research on Cancer. analysis of residential exposure to radon gas A review of human carcinogens: personal and lung cancer. Bull World Health Organ habits and indoor combustions. Tobacco 2003;81(10):732–8. smoking. IARC monographs on the evaluation of carcinogenic risks to humans. Lyon, France: 14 International Agency for Research on Cancer. International Agency for Research on Cancer, Arsenic and arsenic compounds. In: A review 2012. of human carcinogens: arsenic, metals, fibres, and dusts. IARC monographs on the 5 Gandini S, Botteri E, Iodice S, Boniol M, evaluation of carcinogenic risks to humans. Lowenfels AB, Maisonneuve P et al. Tobacco Lyon, France: International Agency for smoking and cancer: a meta-analysis. Int J Research on Cancer, 2012;100C:41–93. Cancer 2008;122(1):155–64. 15 Pershagen G. Lung cancer mortality among 6 Stayner L, Bena J, Sasco AJ, Smith R, men living near an arsenic-emitting smelter. Steenland K, Kreuzer M et al. Lung cancer risk Am J Epidemiol 1985;122(4):684–94. and workplace exposure to environmental tobacco smoke. Am J Public Health 16 Qiao YL, Taylor PR, Yao SX, Erozan YS, 2007;97(3):545–51. Luo XC, Barrett MJ et al. Risk factors and early detection of lung cancer in a cohort 7 Taylor R, Najafi F, Dobson A. Meta-analysis of of Chinese tin miners. Ann Epidemiol studies of passive smoking and lung cancer: 1997;7(8):533–41. effects of study type and continent. Int J Epidemiol 2007;36(5):1048–59. 17 Tsuda T, Nagira T, Yamamoto M, Kurumatani N, Hotta N, Harada M et al. Malignant neoplasms 8 Boffetta P. Involuntary smoking and lung among residents who drank well water cancer. Scand J Work Environ Health contaminated by arsenic from a king’s yellow 2002;28 (suppl 2):30–40. factory. Journal of University of Occupational and Environmental Health 1989;11:289–301. 9 Grosche B, Kreuzer M, Kreisheimer M, Schnelzer M, Tschense A. Lung cancer risk 18 Bosetti C, Boffetta P, La Vecchia C. among German male uranium miners: Occupational exposures to polycyclic a cohort study, 1946–1998. Br J Cancer aromatic hydrocarbons, and respiratory and 2006;95:1280–7. urinary tract cancers: a quantitative review to 2005. Ann Oncol 2007;18(3):431–46. 10 Tomasek L, Rogel A, Tirmarche M, Mitton N, Laurier D. Lung cancer in French and Czech 19 t’Mannetje A, Bencko V, Brennan P, Zaridze D, uranium miners: radon-associated risk at low Szeszenia-Dabrowska N, Rudnai P et al. exposure rates and modifying effects of time Occupational exposure to metal compounds and lung cancer: results from a multi-center
32 Risk factors for lung cancer | An overview of the evidence , Steenland K, Mannetje A, Bofetta P, Stayner L case–control study in Central/Eastern 30 Europe and UK. Cancer Causes Control Attfield M, Chen J et al. Pooled exposure– 2011;22(12):1669–80. response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed 20 Nawrot T, Plusquin M, Hogervorst J, Roels HA, workers: an IARC multicentre study. Cancer Celis H, Thijs L et al. Environmental exposure Causes Control 2001;12(9):773–84. to cadmium and risk of cancer: a prospective population-based study. Lancet Oncol 31 Vida S, Pintos J, Parent ME, Lavoue J, 2006;7(2):119–26. Siemiatycki J. Occupational exposure to silica and lung cancer: pooled analysis of two case– 21 Frost G, Darnton A, Harding AH. The effect of control studies in Montreal, Canada. Cancer smoking on the risk of lung cancer mortality Epidemiol Biomarkers Prev 2010;19(6): for asbestos workers in Great Britain (1971– 1602–11. 2005). Ann Occup Hyg 2011;55(3):239–47. 32 Ahn YS, Won JU, Park RM. Cancer morbidity of 22 International Agency for Research on foundry workers in Korea. J Korean Med Sci Cancer. Asbestos. In: A review of human 2010;25(12):1733–41. carcinogens: arsenic, metals, fibres, and dusts. IARC monographs on the evaluation of 33 Rodriguez V, Tardon A, Kogevinas M, Prieto CS, carcinogenic risks to humans. Lyon, France: Cueto A, Garcia M et al. Lung cancer risk in International Agency for Research on Cancer, iron and steel foundry workers: a nested case 2012;100C 219–309. control study in Asturias, Spain. Am J Ind Med 2000;38(6):644–50. 23 Reid A, de Klerk N, Ambrosini GL, N Olsen N, Pang SC, Berry G et al. The effect of asbestosis 34 Becher H, Jedrychowski W, Flak E, Gomola K, on lung cancer risk beyond the dose related Wahrendorf J. Lung cancer, smoking, and effect of asbestos alone. Occup Environ Med employment in foundries. Scand J Work 2005;62:885–9. Environ Health 1989;15(1):38–42.
24 Erren TC, Morfeld P, Glende CB, Piekarski C, 35 Blot WJ, Brown LM, Pottern LM, Stone BJ, Cocco P. Meta-analyses of published Fraumeni Jr JF. Lung cancer among epidemiological studies, 1979–2006, point long-term steel workers. Am J Epidemiol to open causal questions in silica–silicosis– 1983;117(6):706–16. lung cancer research. La Medicina del Lavoro 2011;102(4):321–35. 36 Beveridge R, Pintos J, Parent ME, Asselin J, Siemiatycki J. Lung cancer risk associated with 25 Pelucchi C, Pira E, Piolatto G, Coggiola M, occupational exposure to nickel, chromium VI, Carta P, La Vecchia C. Occupational silica and cadmium in two population-based case– exposure and lung cancer risk: a review of control studies in Montreal. Am J Ind Med epidemiological studies 1996–2005. Ann 2010;53(5):476–85. Oncol 2006;17(7):1039–50. 37 Grimsrud TK, Berge SR, Martinsen JI, 26 Preller L, van den Bosch LM, van den Brandt Andersen A. Lung cancer incidence among PA, Kauppinen T, Goldbohm A. Occupational Norwegian nickel-refinery workers 1953– exposure to silica and lung cancer risk 2000. J Environ Monit 2003;5(2):190–7. in the Netherlands. Occup Environ Med 2010;67(10):657–63. 38 Ward E, Okun A, Ruder A, Fingerhut M, Steenland K. A mortality study of workers at 27 Lacasse Y, Martin S, Gagne D, Lakhal L. seven beryllium processing plants. Am J Ind Dose–response meta-analysis of silica Med 1992;22(6):885–904. and lung cancer. Cancer Causes Control 2009;20(6):925–33. 39 Levy PS, Roth HD, Hwang PMT, Powers TE. Beryllium and lung cancer: a reanalysis of a 28 Lacasse Y, Martin S, Simard S, Desmeules M. NIOSH cohort mortality study. Inhal Toxicol Meta-analysis of silicosis and lung cancer. 2002;14(10):1003–15. Scand J Work Environ Health 2005;31(6): 450–8. 40 Schubauer-Berigan MK, Couch JR, Petersen MR, Carreon T, Jin Y, Deddens JA. 29 Smith AH, Lopipero PA, Barroga VR. Meta- Cohort mortality study of workers at analysis of studies of lung cancer among seven beryllium processing plants: update silicotics. Epidemiology 1995;6(6):617–24. and associations with cumulative and
Risk factors for lung cancer | An overview of the evidence 33 maximum exposure. Occup Environ Med cancer in a large cohort of never-smokers. Am 2011;68(5):345–53. J Respir Crit Care Med 2011;184(12):1374–81.
41 Sanderson WT, Ward EM, Steenland K, 51 Beelen R, Hoek G, van den Brandt PA, Petersen MR. Lung cancer case–control Goldbohm RA, Fischer P, Schouten LJ et al. study of beryllium workers. Am J Ind Med Long-term exposure to traffic-related air 2001;39(2):133–44. pollution and lung cancer risk. Epidemiology 2008;19(5):702. 42 National Pollutant Inventory. Beryllium and compounds: health effects. Canberra: 52 Raaschou-Nielsen O, Andersen ZJ, Australian Government Department of Hvidberg M, Jensen SS, Ketzel M, Sorensen M Sustainability, Environment, Water, Population et al. Air pollution from traffic and cancer and Communities, 2012. Viewed 5 March incidence: a Danish cohort study. Environ 2012, http://www.npi.gov.au/substances/ Health 2011;10:67. beryllium/health.html. 53 Lissowska J, Foretova L, Dabek J, Zaridze D, 43 Tse LA, Yu IS, Au JS, Qiu H, Wang XR. Silica Szeszenia-Dabrowska N, Rudnai P et al. Family dust, diesel exhaust, and painting work are history and lung cancer risk: international the significant occupational risk factors for multicentre case–control study in Eastern and lung cancer in nonsmoking Chinese men. Br J Central Europe and meta-analyses. Cancer Cancer 2011;104(1):208–13. Causes Control 2010;21(7):1091–104.
44 Guha N, Merletti F, Steenland NK, Altieri A, 54 International Agency for Research on Cancer. Cogliano V, Straif K. Lung cancer risk in Press release no. 213: IARC—diesel exhaust painters: a meta-analysis. Environ Health carcinogenic. Lyon: International Agency for Perspect 2010;118(3):303–12. Research on Cancer, 2012.
45 Bachand A, Mundt KA, Mundt DJ, Carlton LE. 55 Tardon A, Lee WJ, Delgado-Rodriguez M, Meta-analyses of occupational exposure Dosemeci M, Albanes D, Hoover R et al. as a painter and lung and bladder cancer Leisure-time physical activity and lung cancer: morbidity and mortality 1950–2008. Crit Rev a meta-analysis. Cancer Causes Control Toxicol 2010;40(2):101–25. 2005;16(4):389–97.
46 Ramanakumar AV, Parent ME, Richardson L, 56 Sinner P, Folsom AR, Harnack L, Eberly LE, Siemiatycki J. Exposures in painting-related Schmitz KH. The association of physical occupations and risk of lung cancer among activity with lung cancer incidence in a men: results from two case–control studies in cohort of older women: the Iowa Women’s Montreal. Occup Environ Med 2011;68(1): Health Study. Cancer Epidemiol Biomarkers 44–51. Prev 2006;15(12):2359–63.
47 Cole P, Rodu B. Epidemiologic studies of 57 National Health and Medical Research chrome and cancer mortality: a series of Council. NHMRC levels of evidence and meta-analyses. Regul Toxicol Pharmacol grades for recommendations for guideline 2005;43(3):225–31. developers. Canberra: National Health and Medical Research Council, 2009. Viewed 48 Birk T, Mundt KA, Dell LD, Luippold RS, 2 February 2012, http://www.nhmrc.gov. Miksche L, Steinmann-Steiner-Haldenstaett W au/_files_nhmrc/file/guidelines/stage_2_ et al. Lung cancer mortality in the German consultation_levels_and_grades.pdf. chromate industry, 1958 to 1998. J Occup Environ Med 2006;48(4):426–33. 58 Safe Work Australia. Mesothelioma in Australia: incidence 1982 to 2005, deaths 1997 49 Chen H, Goldberg M, Villeneuve P. A to 2006. Canberra: Safe Work Australia, 2009. systematic review of the relation between long-term exposure to ambient air pollution 59 Australian Institute of Health and Welfare, and chronic diseases. Rev Environ Health Australasian Association of Cancer Registries. 2008;23(4):243–97. Cancer in Australia: an overview, 2012. Cancer series no. 74. Cat. no. CAN 70. Canberra: 50 Turner MC, Krewski D, Pope CA III, Chen Y, Australian Institute of Health and Welfare, Gapstur SM, Thun MJ. Long-term ambient 2012. fine particulate matter air pollution and lung
34 Risk factors for lung cancer | An overview of the evidence 60 Australian Institute of Health and Welfare. 70 International Agency for Research on Cancer. Australian Cancer Incidence and Mortality Internalized α-particle emitting radionuclides. books: lung cancer. Canberra: Australian In: A review of human carcinogens: radiation. Institute of Health and Welfare, 2011. Viewed IARC monographs on the evaluation of 21 November, http://www.aihw.gov.au/acim- carcinogenic risks to humans. Lyon, France: books/. International Agency for Research on Cancer, 2012;100D:241–83. 61 Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D. Estimates of worldwide burden of 71 Australian Radiation Protection and Nuclear cancer in 2008: GLOBOCAN 2008. Int J Cancer Safety Agency. Australian National Radiation 2010;127:2893–917. Dose Register: ANRDR fact sheet. Canberra: Australian Radiation Protection and Nuclear 62 Smith S, Campbell N, MacLeod U, Lee A, Safety Agency, 2011. Viewed 12 December Raja A, Wyke S et al. Factors contributing to 2012, http://www.arpansa.gov.au/Services/ the time taken to consult with symptoms of ANRDR/ANRDRFactsheet.cfm. lung cancer: a cross-sectional study. Thorax 2009;64:523–31. 72 Australian Radiation Protection and Nuclear Safety Agency. Radon in homes: fact sheet 63 Australian Institute of Health and Welfare. 5. Canberra: Australian Radiation Protection Cancer survival and prevalence in Australia: and Nuclear Safety Agency, 2011. Viewed period estimates from 1982 to 2010. Cancer 7 December 2012, http://www.arpansa.gov. series no. 69. Cat. No. CAN 65. Canberra: au/radiationprotection/factsheets/is_radon. Australian Institute of Health and Welfare, cfm. 2012. 73 Australian Radiation Protection and Nuclear 64 Australian Institute of Health and Welfare. Safety Agency. Radon map of Australia: fact Australian Cancer Incidence and Mortality sheet 26. Canberra: Australian Radiation books: lung cancer for Australia (ICD10 Protection and Nuclear Safety Agency, C33-C34). Canberra: Australian Institute of 2011. Viewed 7 December 2012, http:// Health and Welfare, 2013. Viewed February, www.arpansa.gov.au/radiationprotection/ http://www.aihw.gov.au/cancer/data/acim_ factsheets/is_RadonMap.cfm. books. 74 Lubin JH, Wang ZY, Boice Jr JD, Xu ZY, Blot WJ, 65 Australian Bureau of Statistics. Australian De Wang L et al. Risk of lung cancer and health survey: first results, 2011–12. Cat. no. residential radon in China: pooled results of 4364.0.55.001. Canberra: Australian Bureau of two studies. Int J Cancer 2004;109(1):132–7. Statistics, 2012. 75 Lagarde F, Axelsson G, Damber L, Mellander H, 66 Lee P. Systematic review of the Nyberg F, Pershagen G. Residential radon epidemiological evidence comparing lung and lung cancer among never-smokers in cancer risk in smokers of mentholated and Sweden. Epidemiology 2001;12(4):396. unmentholated cigarettes. BMC Pulmonary Medicine 2011;11(18):1–28. 76 National Pollutant Inventory. Arsenic and compounds: overview. Canberra: Australian 67 Akl EA, Gaddam S, Gunukula SK, Honeine R, Government Department of Sustainability, Jaoude PA, Irani J. The effects of waterpipe Environment, Water, Population and tobacco smoking on health outcomes: a Communities, 2009. Viewed 7 March 2012, systematic review. Int J Epidemiol 2010;39(3): http://www.npi.gov.au/substances/arsenic/ 834–57. health.html.
68 Boffetta P, Tredaniel J, Greco A. Risk of 77 Tchounwou PB, Patlolla AK, Centeno JA. childhood cancer and adult lung cancer Invited reviews: carcinogenic and systemic after childhood exposure to passive smoke: health effects associated with arsenic a meta-analysis. Environ Health Perspect exposure—a critical review. Toxicol Pathol 2000;108(1):73–82. 2003;31(6):575–88.
69 Al-Zoughool M, Krewski D. Health effects of 78 Hughes JP, Polissar L, Van Belle G. Evaluation radon: a review of the literature. Int J Radiat and synthesis of health effects studies of Biol 2009;85(1):57–69. communities surrounding arsenic producing industries. Int J Epidemiol 1988;17(2):407–13.
Risk factors for lung cancer | An overview of the evidence 35 79 Boffetta P, Jourenkova N, Gustavsson P. Cancer 88 Lugon-Moulin N, Martin F, Krauss MR, risk from occupational and environmental Ramey PB, Rossi L. Cadmium concentration in exposure to polycyclic aromatic hydrocarbons. tobacco (Nicotiana tabacum L.) from different Cancer Causes Control 1997;8(3):473–90. countries and its relationship with other elements. Chemosphere 2006;63(7):1074–86. 80 International Agency for Research on Cancer. Some non-heterocyclic polycyclic aromatic 89 Stayner L, Smith R, Thun M, Schnorr T, hydrocarbons and some related exposures. Lemen R. A dose–response analysis and IARC monographs on the evaluation of quantitative assessment of lung cancer risk carcinogenic risks to humans. Lyon, France: and occupational cadmium exposure. Ann International Agency for Research on Cancer, Epidemiol 1992;2(3):177–94. 2010;92. 90 Adams SV, Passarelli MN, Newcomb PA. 81 International Agency for Research on Cadmium exposure and cancer mortality Cancer. A review of human carcinogens: in the Third National Health and Nutrition chemical agents and related occupations. Examination Survey cohort. Occup Environ IARC monographs on the evaluation of Med 2012;69(2):153–6. carcinogenic risks to humans. Lyon, France: International Agency for Research on Cancer, 91 National Health and Medical Research 2012;100F. Council. Asbestos related diseases. Canberra: National Health and Medical Research Council 82 Friesen MC, Benke G, Del Monaco A, 2011. Viewed 8 December 2011, http://www. Dennekamp M, Fritschi L, de Klerk N et al. nhmrc.gov.au/your-health/asbestos-related- Relationship between cardiopulmonary diseases. mortality and cancer risk and quantitative exposure to polycyclic aromatic 92 Levin 1998, cited in International Agency for hydrocarbons, fluorides, and dust in two Research on Cancer. Asbestos. In: A review prebake aluminum smelters. Cancer Causes of human carcinogens: arsenic, metals, Control 2009;20(6):905–16. fibres, and dusts. IARC monographs on the evaluation of carcinogenic risks to humans. 83 Armstrong B, Tremblay C, Baris D, Theriault G. Lyon, France: International Agency for Lung cancer mortality and polynuclear Research on Cancer, 2012. aromatic hydrocarbons: a case–cohort study of aluminum production workers in Arvida, 93 Valic F. The asbestos dilemma. I. Assessment of Quebec, Canada. Am J Epidemiol 1994;139(3): risk. Arh Hig Rada Toksicol 2002;53:153–67. 250–62. 94 Luce et al 2000, cited in International Agency 84 Armstrong BG, Gibbs G. Exposure–response for Research on Cancer. Asbestos. In: A review relationship between lung cancer and of human carcinogens: arsenic, metals, polycyclic aromatic hydrocarbons (PAHs). fibres, and dusts. IARC monographs on the Occup Environ Med 2009;66(11):740–6. evaluation of carcinogenic risks to humans. Lyon, France: International Agency for 85 Pastorino U, Berrino F, Gervasio A, Pesenti V, Research on Cancer, 2012;100C 219–309. Riboli E, Crosignani P. Proportion of lung cancers due to occupational exposure. Int J 95 Liddell et al 1997 and Piolatto et al 1990, Cancer 1984;33(2):231–7. cited in International Agency for Research on Cancer. Asbestos. In: A review of human 86 International Agency for Research on Cancer. carcinogens: arsenic, metals, fibres, and Cadmium and cadmium compounds. In: A dusts. IARC monographs on the evaluation of review of human carcinogens: arsenic, metals, carcinogenic risks to humans. Lyon, France: fibres, and dusts. IARC monographs on the International Agency for Research on Cancer, evaluation of carcinogenic risks to humans. 2012;100C:219–309. Lyon, France: International Agency for Research on Cancer, 2012;100C:121–45. 96 Wang X, Yano E, Qiu H, Yu I, Courtice MN, Tse LA et al. A 37-year observation of mortality 87 World Health Organization. Cadmium. In: in Chinese chrysotile asbestos workers. Thorax Air quality guidelines for Europe. 2nd edn. 2012;67(2):106–10. Copenhagen: World Health Organization Regional Office for Europe, 2000;136–8. 97 Yano E, Wang X, Wang M, Qiu H, Wang Z. Lung cancer mortality from exposure to chrysotile asbestos and smoking: a case–control study
36 Risk factors for lung cancer | An overview of the evidence within a cohort in China. Occup Environ Med of Occupational and Environmental Medicine 2010;67:867–71. 2009;13(2):65–76.
98 International Agency for Research on Cancer. 108 Hollins DM, McKinley MA, Williams C, Silica, some silicates, coal dust and para- Wiman A, Fillos D, Chapman PS et al. aramid fibrils. IARC monographs on the Beryllium and lung cancer: a weight of evaluation of carcinogenic risks to humans. evidence evaluation of the toxicological and Lyon, France: International Agency for epidemiological literature. Crit Rev Toxicol Research on Cancer, 1997;68:1–506. 2009;39 Suppl 1:1–32.
99 International Agency for Research on Cancer. 109 International Agency for Research on Cancer. Occupational exposures during iron and steel Beryllium and beryllium compounds. In: A founding. In: A review of human carcinogens: review of human carcinogens: arsenic, metals, chemical agents and related occupations. fibres, and dusts. IARC monographs on the IARC monographs on the evaluation of evaluation of carcinogenic risks to humans. carcinogenic risks to humans. Lyon, France: Lyon, France: International Agency for International Agency for Research on Cancer, Research on Cancer, 2012;100C 95–120. 2012;100F:497–507. 110 Australian Bureau of Statistics. Australian 100 Andjelkovich DA, Janszen DB, Brown MH, and New Zealand Standard Classification of Richardson RB, Miller FJ. Mortality of iron Occupations (ANZSCO). Canberra: Australian foundry workers. IV. Analysis of a subcohort Bureau of Statistics, 2012. Viewed 12 April exposed to formaldehyde. Occup Environ 2012, http://www.abs.gov.au/ausstats/abs. Med 1995;37(7):826–37. 111 International Agency for Research on 101 International Agency for Research on Cancer. Cancer. Occupational exposure as a Nickel and nickel compounds. In: A review painter. In: A review of human carcinogens: of human carcinogens: arsenic, metals, chemical agents and related occupations. fibres, and dusts. IARC monographs on the IARC monographs on the evaluation of evaluation of carcinogenic risks to humans. carcinogenic risks to humans. Lyon, France: Lyon, France: International Agency for International Agency for Research on Cancer, Research on Cancer, 2012;100C 169–218. 2012;100F:497–507.
102 Lightfoot NE, Pacey MA, Darling S. Gold, nickel 112 International Agency for Research on Cancer. and copper mining and processing. Chronic Chromium (VI) compounds. In: A review Dis Can 2010;29:2. of human carcinogens: arsenic, metals, fibres, and dusts. IARC monographs on the 103 Grimsrud TK, Peto J. Persisting risk of nickel evaluation of carcinogenic risks to humans. related lung cancer and nasal cancer among Lyon, France: International Agency for Clydach refiners. Occup Environ Med Research on Cancer, 2012;100C 121–45. 2006;63(5):365–6. 113 Fernandez RC, Driscoll TR, Glass DC, 104 Anttila A, Pukkala E, Aitio A, Rantanen T, Vallance D, Reid A, Benke G et al. A priority Karjalainen S. Update of cancer incidence list of occupational carcinogenic agents for among workers at a copper/nickel smelter preventative action in Australia. Aust N Z J and nickel refinery. Int Arch Occup Environ Public Health 2012;36(2):111–5. Health 1998;71(4):245–50. 114 Fritschi L, Driscoll T. Cancer due to occupation 105 Grimsrud TK, Berge SR, Haldorsen T, in Australia. Aust N Z J Public Health Andersen A. Exposure to different forms of 2006;30(3):213–9. nickel and risk of lung cancer. Am J Epidemiol 2002;156(12):1123–32. 115 Stavrides JC. Lung carcinogenesis: pivotal role of metals in tobacco smoke. Free Radic Biol 106 Andersen A, Berge SR, Engeland A, Norseth T. Med 2006;41(7):1017–30. Exposure to nickel compounds and smoking in relation to incidence of lung and nasal 116 Stohs SJ, Bagchi D, Bagchi M. Toxicity of trace cancer among nickel refinery workers. Occup elements in tobacco smoke. Inhal Toxicol Environ Med 1996;53(10):708–13. 1997;9(9):867–90.
107 Cooper RG, Harrison AP. The uses and adverse 117 Boice JD Jr, Marano DE, Fryzek JP, Sadler CJ, effects of beryllium on health. Indian Journal McLaughlin JK. Mortality among aircraft
Risk factors for lung cancer | An overview of the evidence 37 manufacturing workers. Occup Environ Med 127 International Agency for Research on Cancer. 1999;56(9):581–97. Alcohol consumption and ethyl carbamate. IARC monographs on the evaluation of 118 Hara et al 2010, cited in International carcinogenic risks to humans. Lyon, France: Agency for Research on Cancer. Chromium International Agency for Research on Cancer, (VI) compounds. In: A review of human 2010;96. carcinogens: arsenic, metals, fibres, and dusts. IARC monographs on the evaluation of 128 International Agency for Research on Cancer. carcinogenic risks to humans. Lyon, France: Consumption of alcoholic beverages. In: A International Agency for Research on Cancer, review of human carcinogens: personal habits 2012;100C:121–45. and indoor combustions. IARC monographs on the evaluation of carcinogenic risks to 119 van Donkelaar A, Martin RV, Brauer M, humans. Lyon, France: International Agency Kahn R, Levy R, Verduzco C et al. Global for Research on Cancer, 2012;100E:394. estimates of ambient fine particulate matter concentrations from satellite-based aerosol 129 Korte JE, Brennan P, Henley SJ, Boffetta P. optical depth: development and application. Dose-specific meta-analysis and sensitivity Environ Health Perspect 2010;118(6):847–55. analysis of the relation between alcohol consumption and lung cancer risk. Am J 120 Lam TK, Cross AJ, Consonni D, Randi G, Epidemiol 2002;155(6):496–506. Bagnardi V, Bertazzi PA et al. Intakes of red meat, processed meat, and meat mutagens 130 Breslow RA, Graubard BI, Sinha R, Subar AF. increase lung cancer risk. Cancer Res Diet and lung cancer mortality: a 1987 2009;69(3):932–9. National Health Interview Survey cohort study. Cancer Causes Control 2000;11(5):419– 121 Conney et al 1988, cited in Lam TK, Cross AJ, 31. Consonni D, Randi G, Bagnardi V, Bertazzi PA et al. Intakes of red meat, processed meat, 131 Djoussé L, Dorgan JF, Zhang Y, Schatzkin A, and meat mutagens increase lung cancer risk. Hood M, D’Agostino RB et al. Alcohol Cancer Res 2009;69(3):932–9. consumption and risk of lung cancer: the Framingham Study. J Natl Cancer Inst 122 Australian Bureau of Agricultural and 2002;94(24):1877–82. Resource Economics. Australian commodities: September quarter. Canberra: Australian 132 Stemmermann GN, Nomura AMY, Chyou PH, Bureau of Agricultural and Resource Yoshizawa C. Prospective study of alcohol Economics, 2007. intake and large bowel cancer. Dig Dis Sci 1990;35(11):1414–20. 123 Linseisen J, Rohrmann S, Bueno-de-Mesquita B, Buchner FL, Boshuizen HC, Agudo A et 133 Mayne ST, Janerich DT, Greenwald P, al. Consumption of meat and fish and risk Chorost S, Tucci C, Zaman MB et al. Dietary of lung cancer: results from the European beta carotene and lung cancer risk in US Prospective Investigation into Cancer nonsmokers. J Natl Cancer Inst 1994;86(1):33– and Nutrition. Cancer Causes Control 8. 2011;22(6):909–18. 134 Pierce R, Kune G, Kune S, Watson L, Field B, 124 Alavanja MCR, Brownson RC, Benichou J. Merenstein D et al. Dietary and alcohol intake, Estimating the effect of dietary fat on the risk smoking pattern, occupational risk, and of lung cancer in nonsmoking women. Lung family history in lung cancer patients: results Cancer 1996;14(Suppl 1):S63–S74. of a case control study in males. Nutr Cancer 1989;12(3):237–48. 125 De Stefani E, Boffetta P, Deneo-Pellegrini H, Ronco AL, Aune D, Acosta G et al. Meat intake, 135 Shimazu T, Inoue M, Sasazuki S, Iwasaki M, meat mutagens and risk of lung cancer in Kurahashi N, Yamaji T et al. Alcohol and risk Uruguayan men. Cancer Causes Control of lung cancer among Japanese men: data 2009;20(9):1635–43. from a large-scale population-based cohort study, the JPHC study. Cancer Causes Control 126 Australian Institute of Health and Welfare. 2008;19(10):1095–102. 2004 National Drug Strategy household survey: detailed findings. Cat. no. PHE 66. 136 Rachtan J, Sokolowski A. Risk factors for Canberra: Australian Institute of Health and lung cancer among women in Poland. Lung Welfare, 2005. Cancer 1997;18(2):137–45.
38 Risk factors for lung cancer | An overview of the evidence 137 Toriola AT, Kurl S, Laukkanen JA, Kauhanen J. based case–control study. Br Med J Does binge drinking increase the risk of lung 1996;313(7067):1233–5. cancer: results from the Findrink study. Eur J Public Health 2009;19(4):389–93. 149 Morabia A, Stellman S, Lumey LH, Wynder EL. Parakeets, canaries, finches, parrots and 138 Hopkins PN. Effects of dietary cholesterol on lung cancer: no association. Br J Cancer serum cholesterol: a meta-analysis and review. 1998;77(3):501–4. Am J Clin Nutr 1992;55(6):1060–70. 150 Jöckel KH, Pohlabeln H, Bromen K, Ahrens W, 139 International Agency for Research on Cancer. Jahn I. Pet birds and risk of lung cancer Overall evaluations of carcinogenicity: an in north-western Germany. Lung Cancer updating of IARC monographs volumes 1 to 2002;37(1):29–34. 42. IARC monographs on the evaluation of carcinogenic risks to humans. Lyon, France: 151 Kohlmeier L, Arminger G, Bartolomeycik S, International Agency for Research on Cancer, Bellach B, Rehm J, Thamm M. Pet birds as an 1987;Suppl 7. independent risk factor for lung cancer: case– control study. Br Med J 1992;305(6860):986–9. 140 Veierød MB, Laake P, Thelle DS. Dietary fat intake and risk of lung cancer: a prospective 152 Bhatti P, Newcomer L, Onstad L, Teschke K, study of 51,452 Norwegian men and women. Camp J, Morgan M et al. Wood dust exposure Eur J Cancer Prev 1997;6(6):540–9. and risk of lung cancer. Occup Environ Med 2011;68(8):599–604. 141 Smith-Warner SA, Ritz J, Hunter DJ, Albanes D, Beeson WL, Van den Brandt PA et al. Dietary 153 Innos K, Rahu M, Rahu K, Lang I, Leon DA. fat and risk of lung cancer in a pooled analysis Wood dust exposure and cancer incidence: of prospective studies. Cancer Epidemiol a retrospective cohort study of furniture Biomarkers Prev 2002;11(10):987–92. workers in Estonia. Am J Ind Med 2000;37(5):501–11. 142 Hu J, La Vecchia C, de Groh M, Negri E, Morrison H, Mery L. Dietary cholesterol intake 154 Laakkonen A, Kyyronen P, Kauppinen T, and cancer. Ann Oncol 2012;23(2):491–500. Pukkala EI. Occupational exposure to eight organic dusts and respiratory cancer among 143 Jain M, Burch J, Howe G, Risch H, Miller A. Finns. Occup Environ Med 2006;63(11):726– Dietary factors and risk of lung cancer: results 33. from a case-control study, Toronto, 1981– 1985. Int J Cancer 1990;45(2):287–93. 155 Szadkowska-Stańczyk I, Szymczak W. Nested case–control study of lung cancer 144 Ahn J, Lim U, Weinstein SJ, Schatzkin A, among pulp and paper workers in relation Hayes RB, Virtamo J et al. Prediagnostic total to exposure to dusts. Am J Ind Med and high-density lipoprotein cholesterol and 2001;39(6):547–56. risk of cancer. Cancer Epidemiol Biomarkers Prev 2009;18(11):2814–21. 156 Jayaprakash V, Natarajan KK, Moysich KB, Rigual NR, Ramnath N, Natarajan N et al. 145 Keys A, Aravanis C, Blackburn H, Buzina R, Wood dust exposure and the risk of upper Dontas AS, Fidanza F et al. Serum cholesterol aerodigestive and respiratory cancers in and cancer mortality in the Seven Countries males. Occup Environ Med 2008;65(10): Study. Am J Epidemiol 1985;121(6):870–83. 647–54.
146 Chang A, Barrett-Connor E, Edelstein S. Low 157 Stellman SD, Demers PA, Collin D, Boffetta P. plasma cholesterol predicts an increased risk Cancer mortality and wood dust exposure of lung cancer in elderly women. Prev Med among participants in the American Cancer 1995;24(6):557–62. Society Cancer Prevention Study-II (CPS-II). Am J Ind Med 1998;34(3):229–37. 147 Eichholzer M, Stähelin HB, Gutzwiller F, Lüdin E, Bernasconi F. Association of low 158 Australian Government Department of plasma cholesterol with mortality for cancer Health. Physical activity guidelines. Viewed 16 at various sites in men: 17-y follow-up of December 2013, http://www.health.gov.au/ the prospective Basel study. Am J Clin Nutr internet/main/publishing.nsf/Content/health- 2000;71(2):569–74. pubhlth-strateg-phys-act-guidelines.
148 Alavanja MC, Brownson RC, Berger E, Lubin J, Modigh C. Avian exposure and risk of lung cancer in women in Missouri: population
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