AN OVERVIEW OF THE EVIDENCE ON ENVIRONMENTAL AND OCCUPATIONAL DETERMINANTS OF CANCER I.-BACKGROUND AND RATIONALE Cancer is a multifactorial disease due to a combined effect of genetic and external factors acting concurrently and sequentially. Overwhelming evidence indicates that the Cancer is a generic term for a large group of predominant contributor to many types of cancer is the diseases that can affect any part of the body. Other terms environment [9]. This finds support from multi-generation used are malignant tumours and neoplasms. One defining migrants studies showing adoption to the cancer risk of the feature of cancer is the creation of abnormal cells that grow host country [10, 11]. In addition, other studies with beyond their usual boundaries, and which can then invade identical twins have shown the role of the environment in adjoining parts of the body and spread to other organs. This the development of cancer and that genes are not the main process is referred to as metastasis [1]. explanation [12]. For instance, the concordance for breast cancer in twins was found to be only 20% [13]. The Cancer is the second most common cause of death combination of environmental exposures with some gene worldwide after cardiovascular diseases [2, 3]. Globally, polymorphisms may be synergistic and contribute to a there were reported 12.7 million new cases of cancer in substantial proportion of the cancer burden in the general 2008 (6,639,000 in men and 6,038,000 in women) and 7.6 population. million deaths due to cancer (4,225,000 in men and 3,345,000 in women) [4, 5]. Cancer is not a modern disease, The proportion of cancer cases attributable to but as cancer risk increases steeply with age, it is more modifiable risk factors varies greatly across countries, but common nowadays due to increasing life expectancy. It is estimated to always exceed at least one third of cases. has been estimated that the incidence of cancer will double Those cancers would be preventable, therefore the first step between 2000 and 2020 and nearly triple by 2030 [6]. Until in cancer prevention planning is to perform a systematic recently, cancer was considered a disease of westernized, assessment of cancer risk factors at the country level to industrialized countries, however, in 2008, 56% of new obtain good quality and comparable country-level data [14, cases (7.1 millions) and 63% of all cancer deaths (4.8 15]. Annually, roughly 19% (confidence interval 12-29%) millions) were reported by low- and middle-income of all cancers are estimated to be attributable to the countries [4]; this figure is predicted to increase due to a environment, including in work settings, resulting in 1.3 rise in life expectancy of the populations in low- and million deaths [16]. " Environment " is defined by the World middle-income countries and due to their large overall Health Organization (WHO) for the purpose of population size. environmental attribution as " all the physical, chemical and biological factors external to the human host, and all Cancer can impose a substantial burden through related behaviours, but excluding those natural long-term human suffering for individuals and families, environments that cannot reasonably be modified ". This economic impact on active members of society and high definition is in fact limited to those parts of the costs for health-care systems. A recent report showed that environment that can in principle be modified, so as to cancer causes the highest economic loss of all the 15 reduce the health impact of the environment, such as leading causes of death worldwide. The total economic pollution, electromagnetic fields, occupational risks, built impact of premature death and disability from cancer was environments or agricultural methods; and excludes $895 billion in 2008 not including direct costs of treatment. behaviour and life style not related to the environment, The top three cancers that had the highest economic impact such as alcohol and tobacco consumption, as well as globally are lung cancer ($188 billion), colon/rectal cancer behaviour related to the social and cultural environment, ($99 billion) and breast cancer ($88 billion) [7]. Only 5% genetics, and parts of the "unmodifiable" natural of the global resources for cancer are spent in developing environment [16]. Therefore environmental interventions countries [8]. In those countries, cancers are usually are key for reducing the incidence and mortality of cancer, detected at advanced stages, when many are more difficult by eliminating or decreasing the exposure to environmental to treat, therefore treatment interventions are more costly carcinogens, including in work settings, mainly by means and less successful. The estimated rise in cancer incidence of primary prevention measures including individual will have a greater impact on countries that have a low measures of protection. health budget and fragile or absent health systems. 1 Environmental factors that represent risks for the metals, and many by-products of incomplete combustion development of cancer typically affect the general (e.g. dioxins) are all carcinogens that pollute the air [21]. population through exposures that cannot be directly controlled by the individual. These factors can be found in Outdoor air pollution in urban settings the environment as physical (ionizing and non-ionizing radiation such as exposure to radon or ultraviolet (UV) Many of these toxins are released into the air from radiation, respectively), chemical (such as asbestos, dioxins mining operations and other industrial facilities, from the and other pollutants found in industrial emissions and use of coal and other fossil fuels for power generation second-hand smoke, contaminants or natural constituents which is often the case in developed countries, and from found in food and drinking water such as pesticide residues, municipal waste sites and inadequate domestic incineration arsenic or aflatoxins), and biological carcinogens (such as [22]. certain viruses). Carcinogenic effects in human beings result from exposure to radiation, air pollutants, food and Motor vehicles can add significantly to air pollution water components or contaminants, as well as daily in urban areas. Certain substances in vehicles exhaust are consumer exposure from man-made products. These classified as carcinogenic to humans (Group 1) and exposures may occur on multiple occasions and in various probably carcinogenic to humans (Group 2A) by the settings during the course of a life time, from households International Agency for Research on Cancer (IARC) [23]. and schools, to the working environment. Children, Epidemiologic studies have found a higher lung cancer risk including the embryo, fetus, infant and all life stages until among urban residents and persons living near industrial the completion of adolescence are often at greater risk from point sources compared to persons living in rural areas [24]. environmental hazards than adults [17]. Additionally, Large cohort studies on air pollution and mortality have parental occupational exposures may increase the risk of been conducted in several metropolitan areas across the cancer in their offspring. Pesticides, benzene, asbestos and United States, showing a significant increase in mortality ionizing radiation have been investigated [18]. from lung cancer [25, 26]. These findings have been subsequently corroborated in an independent re-analysis Exposure may be widespread, as it is the case for air [27]. pollution, or could be restricted to an area close to a certain industrial site. These exposures have been associated with a Some chemicals such as benzene can also be found variety of neoplasms, but particularly cancer of the lung, in the refuelling emissions near petrol filing stations and skin or leukaemia. Occupational health risks are also inside the vehicles. Benzene has been shown to cause acute directly related to physical, chemical and biological factors myeloid leukaemia and is suggested to be associated with in the environment and frequently related to passive acute and chronic lymphoblastic leukaemia, non-Hodgkin exposures and behaviours. The types of cancer that have lymphoma and multiple myeloma [28]. most commonly been linked with occupational exposures and for which evidence is strong, are those of the lung, Indoor air pollution urinary bladder, mesothelioma, larynx, leukaemia, angiosarcoma of the liver, nose and nasal cavity and skin In most low-income, and many middle-income [19]. countries, the use of coal, wood and other biomass in the home for cooking and heating is very common, leading to high levels of indoor air pollution and contributing also to II.- ENVIRONMENTAL AND OCCUPATIONAL outdoor air pollution. Burning fossil fuels and wood in CARCINOGENS households produce PAHs, increasing the risk of lung cancer and other types of cancers. The use of coal in homes, and to some extent in schools, is especially extensive in 1. CHEMICAL EXPOSURES China where the association between lung cancer in men and women and cooking with open coal stoves has been Historically, the chemical carcinogen or group of shown consistently in multiple studies [29, 30]. The most carcinogens which has received the most attention has been frequent solid fuel used in Asian countries other than China tobacco smoke, and deservedly so. However, there is also is biomass. Although the causal link between biomass fuel strong evidence that industrial and manufacturing use and lung cancer is still considered inconclusive