DOCSLIB.ORG

Alcohol Metabolism and Cancer Risk

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Alcohol Metabolism and Cancer Risk Alcohol Metabolism and Cancer Risk Helmut K. Seitz, M.D., and Peter Becker, M.D. Chronic alcohol consumption increases the risk for cancer of the organs and tissues of the respiratory tract and the upper digestive tract (i.e., upper aerodigestive tract), liver, colon, rectum, and breast. Various factors may contribute to the development (i.e., pathogenesis) of alcohol-associated cancer, including the actions of acetaldehyde, the first and most toxic metabolite of alcohol metabolism. The main enzymes involved in alcohol and acetaldehyde metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are encoded by multiple genes. Because some of these genes exist in several variants (i.e., are polymorphic), and the enzymes encoded by certain variants may result in elevated acetaldehyde levels, the presence of these variants may predispose to certain cancers. Several mechanisms may contribute to alcohol-related cancer development. Acetaldehyde itself is a cancer-causing substance in experimental animals and reacts with DNA to form cancer-promoting compounds. In addition, highly reactive, oxygen-containing molecules that are generated during certain pathways of alcohol metabolism can damage the DNA, thus also inducing tumor development. Together with other factors related to chronic alcohol consumption, these metabolism-related factors may increase tumor risk in chronic heavy drinkers. KEY WORDS: Alcohol and other drug (AOD) consumption; heavy drinking; chronic AOD use; ethanol metabolism; carcinogenesis; cancer; upper respiratory system cancer; oropharyngeal cancer; laryngeal cancer; aerodigestive tract cancer; esophageal cancer; liver cancer; colon cancer; colorectal cancer; breast cancer; acetaldehyde; alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH); genetic factors; cytochrome P450 2E1 (CYP2E1); reactive oxygen species pidemiologic studies of the last bined with smoking, increases the Overall, however, only a small decades have unequivocally iden­ risk of developing these cancers by a percentage of chronic heavy drinkers Etified chronic alcohol consump­ factor of 50 or more, depending on develop certain types of cancer; more­ tion as an important risk factor for the population studied (Pöschl and over, some people develop cancer the development (i.e., pathogenesis) of Seitz 2004). even at relative moderate daily alco­ various types of cancers, including can­ hol consumption. These observations cers of the organs and tissues of the res­ • Alcohol-related liver cancer (i.e., suggest that a genetic predisposition piratory tract and the upper digestive hepatocellular carcinoma) primarily tract (i.e., upper aerodigestive tract), develops in people with liver cirrho­ 1In the United States, a standard drink is frequently defined as the amount of beverage containing 0.5 liver, colon or rectum (i.e., colorectum), sis resulting from chronic excessive ounces, or 14 grams, of pure alcohol. This amount is and breast (for a review, see Bagnardi et alcohol use. found in 12 fluid ounces (fl oz) of beer, 5 fl oz of wine, al. 2001). For these types of cancer, the or 1.5 fl oz of 80-proof distilled spirits. following associations with alcohol • The risk for alcohol-related colorec­ consumption have been found: tal and breast cancer is smaller than HELMUT K. SEITZ, M.D., is a professor that for the upper aerodigestive tract of Medicine and director of the Center • The highest cancer risk associated cancer. However, because these types of Alcohol Research, Liver Disease and with alcohol consumption is seen of cancer have a high prevalence in Nutrition at Salem Medical Center, for the upper aerodigestive tract— the Western world, alcohol likely is University of Heidelberg, Heidelberg, that is, the oral cavity, throat (i.e., an important risk factor. One study Germany. pharynx), voice box (i.e., larynx), (Longnecker 1994) calculated that and esophagus. Heavy drinking 4 percent of all newly diagnosed PETER BECKER, M.D., is a physician in (i.e., consumption of more than breast cancer cases in the United the Department of Medicine, Salem 80 g alcohol, or more than five to States primarily result from alcohol Medical Center, University of Heidelberg, six drinks, per day1), especially com­ consumption. Heidelberg, Germany. 38 Alcohol Research & Health Alcohol Metabolism and Cancer Risk may influence cancer risk. At least part • Cytochrome P450 2E1 (CYP2E1), • For the ALDH2 enzyme, the most of this genetic predisposition may be a protein that is part of the micro­ important enzyme in the metabolism related to alcohol metabolism because somal ethanol oxidizing system of acetaldehyde to acetate, two the rate of alcohol metabolism is genet­ (MEOS) and is involved in alcohol alleles exist, one of which has a very ically determined. Alcohol metabolism metabolism primarily after chronic low activity, resulting in acetalde­ primarily involves three groups of alcohol consumption. hyde accumulation after alcohol enzymes (see Figure) (for more infor­ consumption; this genetic variant mation on the pathways of alcohol For several of these enzymes more is present in a large proportion of metabolism, see Alcohol Research & than one genetic variant exists as fol­ Japanese and other East Asian people. Health Vol. 29, No. 4, “Alcohol lows (for more information, see the Metabolism: Mechanisms of Action”): article by Edenberg, p. 5): • The degree to which CYP2E1 is inducible by chronic alcohol con­ • Alcohol dehydrogenase (ADH) • Two of seven genes encoding ADH sumption varies among people, and enzymes that oxidize beverage alco­ enzymes (i.e., the ADH1B and ADH1C the induction may be genetically hol (i.e., ethanol) to acetaldehyde. genes) show polymorphism—that determined. is, they exist in variants (i.e., alleles) • Aldehyde dehydrogenase (ALDH) that differ in their activities, result­ This review discusses the role of enzymes that oxidize the acetalde­ ing in the generation of different alcohol metabolism in alcohol-associ­ hyde to acetate. quantities of acetaldehyde. ated cancer development (i.e., car­ cinogenesis2), focusing mainly on the contribution of acetaldehyde and on genetic risk factors leading to increased ROS acetaldehyde levels, such as certain alleles of the genes encoding ADH1C Cytochrome DNA-Adducts and ALDH2. This article also briefly P450 2E1 describes the role in carcinogenesis of CYP2E1 and of compounds generated during CYP2E1-mediated alcohol ADH1B*2 ALDH2*1 /2 metabolism. For a discussion of other mechanisms involved in alcohol- ADH1B*1 associated carcinogenesis—such as Ethanol Acetaldehyde Acetate malnutrition with vitamin deficiency, ADH1C*2 ALDH2*1 /1 concomitant smoking, the presence of certain bacteria in the gastroin­ testinal tract (resulting from poor oral ADH1C*1 ALDH2*2 /2 hygiene and diet), and underlying alco­ hol-related diseases—see the recent Microbes review article by Pöschl and Seitz (2004). Figure Pathways of ethanol metabolism and their role in carcinogenesis. Ethanol is oxidized to acetaldehyde through the actions of various alcohol dehy­ Acetaldehyde— drogenase (ADH) enzymes (e.g., enzymes encoded by the ADH1B and A Carcinogen ADH1C genes), through the microsomal enzyme cytochrome P450 2E1 (CYP2E1), and by microbes living in the human gastrointestinal tract (e.g., According to the International Agency mouth and colon). The relative contributions of these pathways and the for Research on Cancer (IARC) (1999), differences in activity between enzymes encoded by different ADH1B overwhelming evidence indicates that and ADH1C alleles is represented by the thickness of the arrows. acetaldehyde should be classified as a Acetaldehyde is oxidized to acetate primarily by the enzyme aldehyde carcinogen in experimental animals. dehydrogenase 2 (ALDH2). Again, the thickness of the arrows indicates For example, acetaldehyde inhalation the rate of acetaldehyde oxidation in people carrying two active ALDH2*1 in rats and hamsters results in cancer alleles, one active ALDH2*1 and one inactive ALDH2*2 allele, or two of the nasal mucosa and the larynx. inactive ALDH2*2 alleles, respectively. Cancer-inducing substances (i.e., carcinogens) generated during the various pathways of alcohol Similarly, long-term administration of metabolism are highlighted. These include acetaldehyde; highly reactive, acetaldehyde in drinking water results oxygen-containing compounds (reactive oxygen species [ROS]) generat­ in changes characterized by excessive ed by CYP2E1; and adducts formed by the interactions of acetaldehyde cell growth of the mucosa cells of the or ROS with DNA. 2For a definition of this and other technical terms used in this article, see the glossary p. 32. Vol. 30, No. 1, 2007 39 upper digestive tract. These mucosal dividing cells, such as the gastroin­ sume sugar (i.e., glucose), these bac­ alterations are similar to those observed testinal mucosa) may react directly teria can produce small amounts of following chronic alcohol ingestion. with acetaldehyde to form a molecule ethanol and acetaldehyde. More Finally, acetaldehyde induces inflam­ called crotonaldehyde, which can bind importantly, if these patients consume mation and transformation of the cells to the DNA and cause mutations alcohol, acetaldehyde concentrations lining the windpipe (i.e., trachea), (Theravathu et al. 2005; Salaspuro et in the stomach increase 6.5-fold interferes with the normal reproduc­ al. 2006). This conversion of acetalde­ (Väkeväinen et al. 2002; Salaspuro tion of cells, and enhances cell injury hyde to crotonaldehyde in the
Load more

Recommended publications
  • State of Science Alcohol and Cancer Fact Sheet
    Alcohol and Cancer Basic description Research shows that alcohol consumption is linked to an increased chance of developing certain cancers. The more alcohol a person consumes, the higher their risk of developing some kinds of cancer. The way alcohol causes cancer isn’t completely understood. It could be that alcohol itself causes cancer by increasing hormone levels, or it may be carcinogenic because of the way it is metabolized, which can make cells more vulnerable to other carcinogens, like tobacco. People who drink heavily and smoke cigarettes or use other kinds of tobacco are at even higher risk for certain cancers. Cancers affected Oral, esophageal, laryngeal, and pharyngeal cancers are more common in alcohol users than in non-alcohol users. Smokers who also drink are at much higher risk. Although the combination of tobacco and alcohol use significantly increases the risk of developing these cancers, alcohol use alone also increases the risk of developing them. Alcohol is also a major cause of liver cancer. Deaths from liver cancer are higher among heavy alcohol users than among people who don’t drink. By altering the liver’s ability to metabolize some carcinogenic substances into harmless compounds or to disable certain existing carcinogens, alcohol’s effects may influence not only liver cancer but other cancers as well. Many studies have found a link between alcohol use and the risk of breast cancer. The risk increases with the amount of alcohol consumed. It’s highest among heavy alcohol users, but even a few drinks a week may increase a person’s risk. Alcohol use has been linked with a higher risk of cancers of the colon and rectum.
    [Show full text]
  • The Impact of Alcohol on Health
    The impact of alcohol on health Peter Anderson Introduction Apart from being a drug of dependence, alcohol has been known for many years as a cause of some 60 different types of disease and condition, including injuries, mental and behavioural disorders, gastrointestinal conditions, cancers, cardiovascular diseases, immunological disorders, lung diseases, skeletal and muscular diseases, reproductive disorders and pre-natal harm, including an increased risk of prematurity and low birth weight (Anderson & Baumberg, 2006). In recent years, overwhelming evidence has confirmed that both the volume of lifetime alcohol use and the combination of frequency of drinking and amount drunk per incident increase the risk of alcohol-related harm, largely in a dose-dependent manner (WHO Regional Office for Europe, 2009; Rehm et al., 2010) with the higher the alcohol consumption, the greater the risk. For some conditions, such as cardiomyopathy, acute respiratory distress syndrome and muscle damage, harm appears only to result from a sustained level of high alcohol consumption, but even at high levels, alcohol increases the risk and severity of these conditions in a dose- dependent manner. The frequency and volume of episodic heavy drinking are of particular importance for increasing the risk of injuries and certain cardiovascular diseases (coronary heart disease and stroke). Although there is a protective effect of light to moderate drinking on ischaemic diseases, overwhelmingly alcohol is toxic to the cardiovascular system. Alcohol is an intoxicant affecting a wide range of structures and processes in the central nervous system which, interacting with personality characteristics, associated behaviour and sociocultural expectations, are causal factors for intentional and unintentional injuries and harm to both the drinker and others.
    [Show full text]
  • References 263
    7. REFERENeES Abel, E.L. (1978) Effect of ethanol on pregnant rats and their offspring. Psychopharmacology,57, 5-11 Abel, E.L. (1979) Sex ratio in fetal alcohol syndrome. Lancet, ii, 105 Abel, E.L. (1980) Fetal alcohol syndrome: behavioral teratology. Psycho 1. Bull., 87, 29-50 Abel, E.L. (1981) Fetal Alcohol Syndrome, VoL. 1, Boca Raton, FL, CRe Press Abel, E.L. (1985a) Prenatal effects of alcohol on growth: a brief overview. Fed. Proc., 44, 2318-2322 Abel, E.L. (1985b) Alcohol enhancement of marijuana-induced fetotoxicity. Teratology, 31, 35-40 Abel, E.L. & Dintcheff, RA. (1978) Effects of prenatal alcohol exposure on growth and development in rats. J. Pharmacol. exp. Ther., 207,916-921 Abel, E.L. & Dintcheff, RA. (1986) Saccharin preference in animaIs prenatally exposed to alcohol: no evidence of altered sexual dimorphism. Neurobehav. Toxicol. Teratol., 8, 521-523 Abel, E.L. & Greizerstein, H.R (1979) Ethanol-induced prenatal growth deficiency: changes in fetal body composition. J. Pharmacol. exp. Ther., 211,668-671 Abernethy, D.J., Frazelle, J. H. & Boreiko, C.J. (1982) Effects of ethanol, acetaldehyde and acetic acid in the C3Hj lOT1j2 CL8 cell transformation system (Abstract No. Bf-l). Environ. Mutagenesis, 4,331 Adam, L. & Postel, W. (1987) Gas chromatographie analysis of ethyl carbamate (urethane) in spirits (GeL). Branntweinwirtschaft, March, 66-68 Addiction Research Foundation (1985) Statistics On Alcohol and Drug Use in Canada and Other Countries, VoL. 1, Statistics on Alcohol Use, Toronto, pp. 214-218 Adelhardt, M., Jensen, O.M. & Hansen, H.S. (1985) Cancer of the larynx, pharynx, and oesophagus in relation to alcohol and tobacco consumption among Danish brewery workers.
    [Show full text]
  • Alcohol Use and Cancer
    cancer.org | 1.800.227.2345 Alcohol Use and Cancer Alcohol use is one of the most important preventable risk factors for cancer, along with tobacco use and excess body weight. Alcohol use accounts for about 6% of all cancers and 4% of all cancer deaths in the United States. Yet many people don’t know about the link between alcohol use and cancer. Cancers linked to alcohol use Alcohol use has been linked with cancers of the: 1 ● Mouth 2 ● Throat (pharynx) 3 ● Voice box (larynx) 4 ● Esophagus 5 ● Liver 6 ● Colon and rectum 7 ● Breast Alcohol probably also increases the risk of cancer of the stomach8, and might affect the risk of some other cancers as well. For each of these cancers, the more alcohol you drink, the higher your cancer risk. But for some types of cancer, most notably breast cancer, consuming even small amounts of alcohol can increase risk. Cancers of the mouth, throat, voice box, and esophagus: Alcohol use clearly raises the risk of these cancers. Drinking and smoking together raises the risk of these cancers many times more than drinking or smoking alone. This might be because alcohol can help harmful chemicals in tobacco get inside the cells that line the mouth, 1 ____________________________________________________________________________________American Cancer Society cancer.org | 1.800.227.2345 throat, and esophagus. Alcohol may also limit how these cells can repair damage to their DNA caused by the chemicals in tobacco. Liver cancer: Long-term alcohol use has been linked to an increased risk of liver cancer. Regular, heavy alcohol use can damage the liver, leading to inflammation and scarring, which might be why it raises the risk of liver cancer.
    [Show full text]
  • Epidemiology of Alcohol and Cancer1
    [CANCER RESEARCH 39, 2840-2843, July1979] 0008-5472/79/0039-0000 $02.00 Epidemiology of Alcohol and Cancer1 A. J. Tuyns International Agency for Research on Cancer, Unit of Epidemiology and Biostatistics, 150 Cours Albert Thomas, 69372 Lyon Cedex 2, France Abstract as Ledermann thought is presently a matter of controversy (2, 3) and will not be discussed here. There is still insufficient knowledge of the distribution of What is undeniable, however, is the need for more surveys drinking habits in human populations, and more descriptive providing a good description of drinking habits in human pop surveysareneeded. ulations. We need to know how people consume alcohol in Both prospective and retrospective epidemiological studies terms of average daily consumption by sex, age, social class, indicate that alcohol consumption is a cancer hazard. Prospec type of drink, rhythm of drinking, and possibly by more param tive studies on excessive drinkers have shown an increased eters. Such a detailed description can only be obtained by risk for cancer of the mouth, pharynx, larynx, esophagus, liver, direct measurement within well-designed surveys. There are and lung. Retrospective studies have confirmed this excess surprisingly few surveys of this kind, and very little is known risk. For cancers of the buccal cavity, pharynx, larynx, and about the way people consume their alcohol throughout the esophagus, the effect of drinking has been shown to be asso world. This is probably the reason why little is known of the ciated with the effect of smoking. In the case of esophageal risks of developing various diseases in relation to alcohol cancer, these two effects are independent, and the observa consumption.
    [Show full text]
  • Epidemiological Studies of Cancer in Humans
    5. EPIDEMIOLOGleAL STUDIES OF eANeER lN HUMANS As early as 1910, it was observed in Paris, France, that about 80% of patients with cancer of the oesophagus and cardiac region of the stomach were alcoholics, who drank mainly absinthe (Lamy, 1910). ln the first half of this century, it was also noted from mortality statistics in various countries that high risks for cancers of the oral cavity, pharynx, oesophagus and larynx occurred among persons employed in the production and distribution of alcoholIc beverages (Young & RusselI, 1926; Clemmesen, 1941; Kennaway & Kennaway, 1947; Versluys, 1949). Later studies showed that cancers at these sites occur at lower rates of incidence (and mortality) in religious groups that proscribe alcohol intake, such as Seventh-day Adventists (Wynder et aL., 1959; Lemon et al., 1964; Philips et al., 1980), compared with corresponding national populations. Although many aspects of the life style of such populations are particular, differences in drinking (and smoking) habits may contribute to the differences in disease rates. Subsequent to these historical observations and studies of religious groups, analytical studies of the cohort and case- control type have been carried out. 5.1 Measurement of alcohol intake in epidemiological studies ln descriptive studies, discussed below, a very crude level of a1cohol intake is typically inferred for a group of individuals, on the basis of characteristics such as treatment for a1coholism. Frequently, even measurements of average a1cohol intake in these groups and in the groups with which they are compared are not avaIlable. ln case-control and cohort studies involving individual subjects, measurements of a1cohol intake are usually obtained by structured interview or questionnaire.
    [Show full text]
  • Alcohol and Cancer Risk
    ALCOHOL AND HEALTH ALCOHOL AND CANCER RISK TABLE OF CONTENTS Preface 1 Introduction 2 Alcohol use and relative cancer risk 3 How alcohol acts on the body to affect cancer risk 6 Risk factors affecting the association between alcohol and cancer 8 Effects of alcohol according to drinking profile 10 Conclusion 12 978-2-924784-47-1 Legal Deposit - Bibliothèque et Archives nationales du Québec, 2018 Legal Deposit - Library and Archives Canada, 2018 ALCOHOL AND HEALTH ALCOHOL AND CANCER RISK 1 PREFACE A recent Éduc’alcool survey on Quebecers and Nevertheless, the subject of alcohol and cancer alcohol revealed that one in ten drinkers felt that risk is particularly charged, because of the fear that drinking was affecting their physical health. More the disease still evokes and the strong emotions it than a third of all respondents (37%) believe that arouses. It’s a fact that one in two Quebecers will health issues are the main problem related to be affected by cancer at some point during their alcohol abuse. It is therefore easy to understand lifetime, and that many myths about cancer are still why nearly two-thirds of Quebecers put health at widely believed. the top of the list of topics of interest with regard to drinking. It is therefore extremely important to provide comprehensive, serious and solidly founded This is no surprise. The media report regularly on information about the relationship between alcohol the results of studies on the impact of alcohol on and cancer risk. Furthermore, the information must human health, because an ever-increasing amount be presented calmly, it must distinguish relative of research is demonstrating the benefits and risks risk from absolute risk, and it must neither trivialize of different amounts of alcohol and approaches to nor terrorize.
    [Show full text]
  • Alcohol Use in Midlife Women
    Alcohol Use in Midlife Women Connie B. Newman MD, FACP, FAMWA 2018 President, American Medical Women’s Association Adjunct Professor of Medicine Division of Endocrinology, Diabetes and Metabolism New York University School of Medicine [email protected] Disclosures • No disclosures Connie Newman MD Questions • What is known about prevalence of alcohol use, binge drinking, and alcohol use disorder by age and sex? • What is the underlying problem? Why is (alcohol) drinking increasing in middle age women? • How is alcohol metabolized? Is this different in women? • What are health risks? Health benefits? • How can we screen for alcohol problems? • What are treatment options? WHAT CAN CLINICIANS DO TO ADDRESS THIS PROBLEM? Connie Newman MD • Alcohol use disorder (AUD) is not a “moral failing”, but rather a chronic disease with a neurobiological basis • Public and self stigma associated with AUD or excessive drinking is counterproductive • Much of the data available are based on interviews, and therefore may underestimate the magnitude of the disease. Connie Newman MD A Tale of Two Cities Paris 1875-6 London 1751 “Absinthe Drinker” by Edgar Degas “Gin Lane” by William Hogarth Connie Newman MD What is one standard drink? USA: National Institute on Alcohol Abuse and Alcoholism (NIAAA) CANADA: https://www.rethin kyourdrinking.ca/ what-is-a- standard-drink/ Connie Newman MD Low risk drinking, in U.S. https://www.rethinkingdrinking.niaaa.nih.gov/How-much-is-too-much/Is-your- drinking-pattern-risky/whats-Low-Risk-drinking.aspx Connie Newman MD Prevalence Global data 2016 • 32.5% or 2.4 billion people were current drinkers o 25% women o 39% men • Varies by location and by sex • Lowest in low sociodemographic groups • 2.8 million deaths attributed to alcohol o 2.2% of deaths in women o 6.8% of deaths in men GBD 2016 Alcohol Collaborators.
    [Show full text]
  • Awareness of the Link Between Alcohol Consumption and Cancer Across the World: a Review
    Review Cancer Epidemiology, Biomarkers Awareness of the Link between Alcohol & Prevention Consumption and Cancer across the World: A Review Jennifer K. Scheideler and William M.P. Klein Abstract Since 1988, the International Agency for Research on Cancer ally; it is relatively higher in the United Kingdom, Morocco, and has classified alcohol as a Group 1 carcinogen, the highest level Australia. Methodologic differences in assessment obfuscate of risk. Growing evidence suggests that alcohol increases the cross-country and cross-sample comparisons. In general, peo- risk of several types of cancer including breast, bowel, prostate, ple are more likely to endorse alcohol as a risk factor when and liver, and accounts for a significant proportion of prevent- presented with a list of possible risk factors than when asked to able cancers. Despite ample evidence of this relationship, list risk factors in an open-ended format. Attempts to increase publicawarenessislessclear.FollowingPreferredReporting awareness have been limited and constitute a significant public Items for Systematic Reviews and Meta-Analyses (PRISMA) health need. We provide potential strategies to increase aware- guidelines, we reviewed 32 studies examining lay awareness ness, such as alcohol bottle labeling and fostering patient/ of alcohol as a risk factor for cancer in 16 countries. Our results physician discussions regarding the link. Cancer Epidemiol Biomar- show that awareness appears to be low and varies internation- kers Prev; 27(4); 429–37. Ó2018 AACR. Introduction cancer risk is also relatively higher among those who con- sume relatively small amounts of alcohol (16, 17). Nelson and Alcohol accounts for 4.65% of the global burden of injury colleagues (2013) (18) estimate that 31% to 51% of alcohol- and disease, making it one of the most preventable causes of related cancer cases occurred among women who consumed injury and death (1, 2), and an important behavioral risk factor 20 grams or less (approximately 1.5 drinks) per day.
    [Show full text]
  • Moderate Alcohol Intake in Non-Alcoholic Fatty Liver Disease: to Drink Or Not to Drink?
    nutrients Review Moderate Alcohol Intake in Non-Alcoholic Fatty Liver Disease: To Drink or Not to Drink? Maria L. Petroni * , Lucia Brodosi, Francesca Marchignoli, Alessandra Musio and Giulio Marchesini * Department of Medical and Surgical Sciences, “Alma Mater” University, Sant’Orsola-Malpighi Hospital, Via Massarenti 9, 1-40135 Bologna, Italy; [email protected] (L.B.); [email protected] (F.M.); [email protected] (A.M.) * Correspondence: [email protected] (M.L.P.); [email protected] (G.M.) Received: 31 October 2019; Accepted: 10 December 2019; Published: 13 December 2019 Abstract: Nonalcoholic fatty liver disease (NAFLD) is defined by hepatic steatosis in the presence of alcohol intake within safe limits, defined by guidelines of scientific associations (usually 20 g or 2 units/day in women, 30 g or 3 units in men). The diagnosis is usually followed by medical counseling of total abstinence, in order to prevent disease progression. This policy has been challenged by epidemiological studies, suggesting that the risk of liver disease and disease progression is lower in modest drinkers than in total abstainers. We revised the literature on the effects of modest alcohol intake on disease burden. Epidemiological data may suffer from several potential biases (recall bias for retrospective analyses, difficulties in the calculation of g/day), limiting their validity. Prospective data suggest that NAFLD patients with regular alcohol intake, although within the safe thresholds, are at higher risk of liver disease progression, including hepatocellular carcinoma; a detrimental effect of modest alcohol drinking is similarly observed in liver disease of viral etiology. Alcohol intake is also a risk factor for extrahepatic cancers, particularly breast, oral, and pharyngeal cancers, with gender difference and no floor effect, which outweigh the possible beneficial effects on cardiovascular system, also derived from retrospective studies.
    [Show full text]
  • Alcoholic Drinks and the Risk of Cancer: a Summary Matrix 7 2
    Alcoholic drinks and the risk of cancer 2018 Contents World Cancer Research Fund Network 3 Executive summary 5 1. Alcoholic drinks and the risk of cancer: a summary matrix 7 2. Summary of Panel judgements 9 3. Definitions and patterns 10 3.1 Alcoholic drinks 10 3.2 Types of alcoholic drinks 12 4. Interpretation of the evidence 13 4.1 General 13 4.2 Specific 13 5. Evidence and judgements 24 5.1 Alcoholic drinks 24 6. Comparison with the 2007 Second Expert Report 59 Acknowledgements 60 Abbreviations 64 Glossary 65 References 71 Appendix 1: Criteria for grading evidence for cancer prevention 78 Appendix 2: Mechanisms 81 Our Cancer Prevention Recommendations 84 2 Alcoholic drinks and the risk of cancer 2018 WORLD CANCER RESEARCH FUND NETWORK Our Vision We want to live in a world where no one develops a preventable cancer. Our Mission We champion the latest and most authoritative scientific research from around the world on cancer prevention and survival through diet, weight and physical activity, so that we can help people make informed choices to reduce their cancer risk. As a network, we influence policy at the highest level and are trusted advisors to governments and to other official bodies from around the world. Our Network World Cancer Research Fund International is a not-for-profit organisation that leads and unifies a network of cancer charities with a global reach, dedicated to the prevention of cancer through diet, weight and physical activity. The World Cancer Research Fund network of charities is based in Europe, the Americas and Asia, giving us a global voice to inform people about cancer prevention.
    [Show full text]
  • Cocarcinogenic Effects of Alcohol in Hepatocarcinogenesis
    132 REVIEW Cocarcinogenic effects of alcohol in Gut: first published as 10.1136/gut.51.1.132 on 1 July 2002. Downloaded from hepatocarcinogenesis F Stickel, D Schuppan, E G Hahn, H K Seitz ............................................................................................................................. Gut 2002;51:132–139 Alcohol is a major aetiological factor in INTRODUCTION hepatocarcinogenesis but our understanding of its Hepatocellular carcinoma (HCC) is the most frequent primary liver tumour among the com- importance as a modulating factor is just beginning to monest malignant tumours today.1 Its prevalence emerge. In the present review, a number of possible is increasing worldwide but differs greatly be- cofactors and mechanisms are discussed by which tween regions, with incidences of approximately 3–4/100 000 in Western countries2–4 and up to alcohol may enhance the development of hepatoma. 120/100 000 in Asia and Southern Africa. In more These include dietary or environmental carcinogens than 80% of European and North American cases, ingested along with alcoholic beverages, alcoholic HCCs develop in cirrhotic livers whereas in Asia near 50% of HCCs may occur in non-cirrhotic cirrhosis as a precancerous condition, and the effects of livers.56The increase in HCC is most likely due to alcohol metabolism. the more widespread chronic infection with .......................................................................... hepatotropic viruses, namely hepatitis B (HBV) and especially hepatitis C (HCV). Epidemiological studies have incriminated both viruses in hepato- SUMMARY carcinogenesis, and the contributory role of alco- The incidence of hepatocellular carcinoma is ris- hol, a major aetiological factor of liver cirrhosis in ing worldwide. Apart from hepatitis B and C Western countries, is undisputed.1 In the follow- viruses, alcohol presents a major aetiological fac- ing, we summarise the evidence and discuss tor in hepatocarcinogenesis, as shown in numer- potential mechanisms of the cocarcinogenic effect ous epidemiological studies.
    [Show full text]