Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis

V Bagnardi, M Rota, E Botteri, I Tramacere, F Islami, V Fedirko, L Scotti, M Jenab, F Turati, E Pasquali, C Pelucchi, C Galeone, R Bellocco, E Negri, G Corrao, P Boffetta, C La Vecchia, V Bagnardi, M Rota, E Botteri, I Tramacere, F Islami, V Fedirko, L Scotti, M Jenab, F Turati, E Pasquali, C Pelucchi, C Galeone, R Bellocco, E Negri, G Corrao, P Boffetta, C La Vecchia

Abstract

Background: Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial.

Methods: We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose-response meta-regression models and investigated potential sources of heterogeneity.

Results: A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose-risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated.

Conclusions: Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.

Figures

Figure 1
Figure 1
Flowchart of selection of studies for inclusion in meta-analysis.
Figure 2
Figure 2
Pooled RR estimates by cancer site and alcohol intake. Squares indicate the RR estimates and whiskers their 95% confidence intervals. Abbreviations: AC=adenocarcinoma; CI= confidence interval; RR= relative risk; SCC=squamous cell carcinoma.
Figure 3
Figure 3
Relative risk functions and corresponding 95% confidence intervals describing the dose–response relationship between alcohol consumption and cancer risk obtained by fitting meta-regression models, by cancer site. Abbreviations: AC=adenocarcinoma; RR=relative risk; SCC=squamous cell carcinoma.
Figure 3
Figure 3
Relative risk functions and corresponding 95% confidence intervals describing the dose–response relationship between alcohol consumption and cancer risk obtained by fitting meta-regression models, by cancer site. Abbreviations: AC=adenocarcinoma; RR=relative risk; SCC=squamous cell carcinoma.

References

    1. Altieri A, La Vecchia C, Negri E. Fluid intake and risk of bladder and other cancers. Eur J Clin Nutr. 2003;57 (Suppl 2:S59–S68.
    1. Bagnardi V, Blangiardo M, La Vecchia C, Corrao G. A meta-analysis of alcohol drinking and cancer risk. Br J Cancer. 2001;85:1700–1705.
    1. Bagnardi V, Rota M, Botteri E, Scotti L, Jenab M, Bellocco R, Tramacere I, Pelucchi C, Negri E, La Vecchia C, Corrao G, Boffetta P. Alcohol consumption and lung cancer risk in never smokers: a meta-analysis. Ann Oncol. 2011;22 (12:2631–2639.
    1. Bagnardi V, Rota M, Botteri E, Tramacere I, Islami F, Fedirko V, Scotti L, Jenab M, Turati F, Pasquali E, Pelucchi C, Bellocco R, Negri E, Corrao G, Rehm J, Boffetta P, La Vecchia C. Light alcohol drinking and cancer: a meta-analysis. Ann Oncol. 2013;24 (2:301–308.
    1. Bagnardi V, Zatonski W, Scotti L, La Vecchia C, Corrao G. Does drinking pattern modify the effect of alcohol on the risk of coronary heart disease? Evidence from a meta-analysis. J Epidemiol Community Health. 2008;62 (7:615–619.
    1. Bellocco R, Pasquali E, Rota M, Bagnardi V, Tramacere I, Scotti L, Pelucchi C, Boffetta P, Corrao G, La Vecchia C. Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis. Ann Oncol. 2012;23 (9:2235–2244.
    1. Berlin JA, Longnecker MP, Greenland S. Meta-analysis of epidemiologic dose response data. Epidemiology. 1993;4 (3:218–228.
    1. Boffetta P, Hashibe M. Alcohol and cancer. Lancet Oncol. 2006;7 (2:149–156.
    1. Boffetta P, Hashibe M, La Vecchia C, Zatonski W, Rehm J. The burden of cancer attributable to alcohol drinking. Int J Cancer. 2006;119 (4:884–887.
    1. Boniol M, Autier P. Prevalence of main cancer lifestyle risk factors in Europe in 2000. Eur J Cancer. 2010;46 (14:2534–2544.
    1. Boyle P, Boffetta P, Lowenfels A, Burns Harry, Brawley Otis, Zatonski Witold, Rehm Jürgen.(eds) (2013Alcohol: Science, Policy and Public Health Oxford University Press: Oxford
    1. Brewin TB. Alcohol intolerance in neoplastic disease. Br Med J. 1966;2:437–441.
    1. Bryant AJ, Newman JH. Alcohol intolerance associated with Hodgkin lymphoma. CMAJ. 2013;185 (8:E353.
    1. Cai S, Li Y, Ding Y, Chen K, Jin M. Alcohol drinking and the risk of colorectal cancer death: a meta-analysis. Eur J Cancer Prev. 2014;23 (6:532–539.
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188.
    1. Doll R, Forman D, La Vecchia C, Woutersen R.1999Alcoholic beverages and cancers of the digestive tract and larynx Health Issues Related to Alcohol Consumption2nd edn351–393.Blackwell: Oxford
    1. Fedirko V, Tramacere I, Bagnardi V, Rota M, Scotti L, Islami F, Negri E, Straif K, Romieu I, La Vecchia C, Boffetta P, Jenab M. Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. Ann Oncol. 2011;22 (9:1958–1972.
    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–2917.
    1. Ferrari P, Jenab M, Norat T, Moskal A, Slimani N, Olsen A, Tjønneland A, Overvad K, Jensen MK, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Rohrmann S, Linseisen J, Boeing H, Bergmann M, Kontopoulou D, Trichopoulou A, Kassapa C, Masala G, Krogh V, Vineis P, Panico S, Tumino R, van Gils CH, Peeters P, Bueno-de-Mesquita HB, Ocké MC, Skeie G, Lund E, Agudo A, Ardanaz E, López DC, Sanchez MJ, Quirós JR, Amiano P, Berglund G, Manjer J, Palmqvist R, Van Guelpen B, Allen N, Key T, Bingham S, Mazuir M, Boffetta P, Kaaks R, Riboli E. Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC) Int J Cancer. 2007;121 (9:2065–2072.
    1. Galeone C, Malerba S, Rota M, Bagnardi V, Negri E, Scotti L, Bellocco R, Corrao G, Boffetta P, La Vecchia C, Pelucchi C. A meta-analysis of alcohol consumption and the risk of brain tumours. Ann Oncol. 2013;24 (2:514–523.
    1. Goedde HW, Agarwal DP, Fritze G, Meier-Tackmann D, Singh S, Beckmann G, Bhatia K, Chen LZ, Fang B, Lisker R, Paik YK, Rothhammer F, Saha N, Segal B, Srivastava LM, Czeizel A. Distribution of ADH2 and ALDH2 genotypes in different populations. Hum Genet. 1992;88:344–346.
    1. Greenland S.1987Quantitative methods in the review of epidemiologic literature Epidemiol Rev 91–30.1-30.
    1. Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol. 1992;135:1301–1309.
    1. Hamajima N, Hirose K, Tajima K, Rohan T, Calle EE, Heath CW, Jr, Coates RJ, Liff JM, Talamini R, Chantarakul N, Koetsawang S, Rachawat D, Morabia A, Schuman L, Stewart W, Szklo M, Bain C, Schofield F, Siskind V, Band P, Coldman AJ, Gallagher RP, Hislop TG, Yang P, Kolonel LM, Nomura AM, Hu J, Johnson KC, Mao Y, De Sanjosé S, Lee N, Marchbanks P, Ory HW, Peterson HB, Wilson HG, Wingo PA, Ebeling K, Kunde D, Nishan P, Hopper JL, Colditz G, Gajalanski V, Martin N, Pardthaisong T, Silpisornkosol S, Theetranont C, Boosiri B, Chutivongse S, Jimakorn P, Virutamasen P, Wongsrichanalai C, Ewertz M, Adami HO, Bergkvist L, Magnusson C, Persson I, Chang-Claude J, Paul C, Skegg DC, Spears GF, Boyle P, Evstifeeva T, Daling JR, Hutchinson WB, Malone K, Noonan EA, Stanford JL, Thomas DB, Weiss NS, White E, Andrieu N, Brêmond A, Clavel F, Gairard B, Lansac J, Piana L, Renaud R, Izquierdo A, Viladiu P, Cuevas HR, Ontiveros P, Palet A, Salazar SB, Aristizabel N, Cuadros A, Tryggvadottir L, Tulinius H, Bachelot A, Lê MG, Peto J, Franceschi S, Lubin F, Modan B, Ron E, Wax Y, Friedman GD, Hiatt RA, Levi F, Bishop T, Kosmelj K, Primic-Zakelj M, Ravnihar B, Stare J, Beeson WL, Fraser G, Bullbrook RD, Cuzick J, Duffy SW, Fentiman IS, Hayward JL, Wang DY, McMichael AJ, McPherson K, Hanson RL, Leske MC, Mahoney MC, Nasca PC, Varma AO, Weinstein AL, Moller TR, Olsson H, Ranstam J, Goldbohm RA, van den Brandt PA, Apelo RA, Baens J, de la Cruz JR, Javier B, Lacaya LB, Ngelangel CA, La Vecchia C, Negri E, Marubini E, Ferraroni M, Gerber M, Richardson S, Segala C, Gatei D, Kenya P, Kungu A, Mati JG, Brinton LA, Hoover R, Schairer C, Spirtas R, Lee HP, Rookus MA, van Leeuwen FE, Schoenberg JA, McCredie M, Gammon MD, Clarke EA, Jones L, Neil A, Vessey M, Yeates D, Appleby P, Banks E, Beral V, Bull D, Crossley B, Goodill A, Green J, Hermon C, Key T, Langston N, Lewis C, Reeves G, Collins R, Doll R, Peto R, Mabuchi K, Preston D, Hannaford P, Kay C, Rosero-Bixby L, Gao YT, Jin F, Yuan JM, Wei HY, Yun T, Zhiheng C, Berry G, Cooper Booth J, Jelihovsky T, MacLennan R, Shearman R, Wang QS, Baines CJ, Miller AB, Wall C, Lund E, Stalsberg H, Shu XO, Zheng W, Katsouyanni K, Trichopoulou A, Trichopoulos D, Dabancens A, Martinez L, Molina R, Salas O, Alexander FE, Anderson K, Folsom AR, Hulka BS, Bernstein L, Enger S, Haile RW, Paganini-Hill A, Pike MC, Ross RK, Ursin G, Yu MC, Longnecker MP, Newcomb P, Bergkvist L, Kalache A, Farley TM, Holck S, Meirik O, Collaborative Group on Hormonal Factors in Breast Cancer Alcohol, tobacco and breast cancer—collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer. 2002;87 (11:1234–1245.
    1. Hamid A, Wani NA, Kaur J. New perspectives on folate transport in relation to alcoholism-induced folate malabsorption—association with epigenome stability and cancer development. FEBS J. 2009;276 (8:2175–2191.
    1. Hamling J, Lee P, Weitkunat R, Ambuhl M. Facilitating meta-analyses by deriving relative effect and precision estimates for alternative comparisons from a set of estimates presented by exposure level or disease category. Stat Med. 2008;27:954–970.
    1. Heinen MM, Verhage BA, Schouten LJ, Goldbohm RA, Schouten HC, van den Brandt PA. Alcohol consumption and risk of lymphoid and myeloid neoplasms: results of the Netherlands cohort study. Int J Cancer. 2013;133 (7:1701–1712.
    1. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558.
    1. IARC Working Group . IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Alcohol Drinking. International Agency for Research on Cancer: Lyon; 1988.
    1. IARC Working Group . IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: A Review of Human Carcinogens: Personal Habits and Indoor Combustions. International Agency for Research on Cancer: Lyon; 2010.
    1. Islami F, Fedirko V, Tramacere I, Bagnardi V, Jenab M, Scotti L, Rota M, Corrao G, Garavello W, Schüz J, Straif K, Negri E, Boffetta P, La Vecchia C. Alcohol drinking and esophageal squamous cell carcinoma with focus on light-drinkers and never-smokers: a systematic review and meta-analysis. Int J Cancer. 2011;129 (10:2473–2484.
    1. Islami F, Tramacere I, Rota M, Bagnardi V, Fedirko V, Scotti L, Garavello W, Jenab M, Corrao G, Straif K, Negri E, Boffetta P, La Vecchia C. Alcohol drinking and laryngeal cancer: overall and dose-risk relation—a systematic review and meta-analysis. Oral Oncol. 2010;46 (11:802–810.
    1. Kiechl S, Willeit J, Poewe W, Egger G, Oberhollenzer F, Muggeo M, Bonora E. Insulin sensitivity and regular alcohol consumption: large, prospective, cross sectional population study (Bruneck study) BMJ. 1996;313 (7064:1040–1044.
    1. Klatsky AL. Diet, alcohol, and health: a story of connections, confounders, and cofactors. Am J Clin Nutr. 2001;74:279–280.
    1. La Vecchia C, Bosetti C, Bertuccio P, Castro C, Pelucchi C, Negri E. Trends in alcohol consumption in Europe and their impact on major alcohol-related cancers. Eur J Cancer Prev. 2014;23 (4:319–322.
    1. Lamy L. Étude clinique et statistique de 134 cas de cancer de l'oesophage et du cardia. Arch Mal App Dig. 1910;4:451–475.
    1. Lee JE, Hunter DJ, Spiegelman D, Adami HO, Albanes D, Bernstein L, van den Brandt PA, Buring JE, Cho E, Folsom AR, Freudenheim JL, Giovannucci E, Graham S, Horn-Ross PL, Leitzmann MF, McCullough ML, Miller AB, Parker AS, Rodriguez C, Rohan TE, Schatzkin A, Schouten LJ, Virtanen M, Willett WC, Wolk A, Zhang SM, Smith-Warner SA. Alcohol intake and renal cell cancer in a pooled analysis of 12 prospective studies. J Natl Cancer Inst. 2007;99 (10:801–810.
    1. Liang H, Wang J, Xiao H, Wang D, Wei W, Qiao Y, Boffetta P. Estimation of cancer incidence and mortality attributable to alcohol drinking in China. BMC Public Health. 2010;10:730.
    1. Martinez I. Factors associated with cancer of the esophagus, mouth, and pharynx in Puerto Rico. J Natl Cancer Inst. 1969;42:1069–1094.
    1. McGregor SE, Courneya KS, Kopciuk KA, Tosevski C, Friedenreich CM. Case-control study of lifetime alcohol intake and prostate cancer risk. Cancer Causes Control. 2013;24 (3:451–461.
    1. Mukherji B. Immunology of melanoma. Clin Dermatol. 2013;31 (2:156–165.
    1. Nelson DE, Jarman DW, Rehm J, Greenfield TK, Rey G, Kerr WC, Miller P, Shield KD, Ye Y, Naimi TS. Alcohol-attributable cancer deaths and years of potential life lost in the United States. Am J Public Health. 2013;103 (4:641–648.
    1. Newsholme A. The possible association of the consumption of alcohol with excessive mortality from cancer. Br Med J. 1903;2 (2241:1529–1531.
    1. Olsen J, Sabreo S, Fasting U. Interaction of alcohol and tobacco as risk factors in cancer of the laryngeal region. J Epidemiol Community Health. 1985;39 (2:165–168.
    1. Oze I, Matsuo K, Wakai K, Nagata C, Mizoue T, Tanaka K, Tsuji I, Sasazuki S, Inoue M, Tsugane S, Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan Alcohol drinking and esophageal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2011;41:677–692.
    1. Pelucchi C, Galeone C, Tramacere I, Bagnardi V, Negri E, Islami F, Scotti L, Bellocco R, Corrao G, Boffetta P, La Vecchia C. Alcohol drinking and bladder cancer risk: a meta-analysis. Ann Oncol. 2012;23 (6:1586–1593.
    1. Pöschl G, Seitz HK. Alcohol and cancer. Alcohol Alcohol. 2004;39 (3:155–165.
    1. R Development Core Team 2008. R: A language and environment for statistical computing. R Foundation for Statistical Computing: Vienna, Austria. .
    1. Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet. 2009;373 (9682:2223–2233.
    1. Rota M, Bellocco R, Scotti L, Tramacere I, Jenab M, Corrao G, La Vecchia C, Boffetta P, Bagnardi V. Random-effects meta-regression models for studying nonlinear dose-response relationship, with an application to alcohol and esophageal squamous cell carcinoma. Stat Med. 2010;29 (26:2679–2687.
    1. Rota M, Pasquali E, Scotti L, Pelucchi C, Tramacere I, Islami F, Negri E, Boffetta P, Bellocco R, Corrao G, La Vecchia C, Bagnardi V. Alcohol drinking and epithelial ovarian cancer risk. a systematic review and meta-analysis. Gynecol Oncol. 2012;125 (3:758–763.
    1. Rota M, Scotti L, Turati F, Tramacere I, Islami F, Bellocco R, Negri E, Corrao G, Boffetta P, La Vecchia C, Bagnardi V. Alcohol consumption and prostate cancer risk: a meta-analysis of the dose-risk relation. Eur J Cancer Prev. 2012;21 (4:350–359.
    1. Saladi RN, Nektalova T, Fox JL. Induction of skin carcinogenicity by alcohol and ultraviolet light. Clin Exp Dermatol. 2010;35 (1:7–11.
    1. Sawada N, Inoue M, Iwasaki M, Sasazuki S, Yamaji T, Shimazu T, Tsugane S. Alcohol and smoking and subsequent risk of prostate cancer in Japanese men: the Japan public health center-based prospective study (JPHC Study) Int J Cancer. 2014;134 (4:971–978.
    1. Seitz HK, Pelucchi C, Bagnardi V, La Vecchia C. Epidemiology and pathophysiology of alcohol and breast cancer: update 2012. Alcohol Alcohol. 2012;47 (3:204–212.
    1. Seitz HK, Stickel F. Molecular mechanisms of alcohol-mediated carcinogenesis. Nat Rev Cancer. 2007;7 (8:599–612.
    1. Singletary KW, Gapstur SM. Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms. JAMA. 2001;286 (17:2143–2151.
    1. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283 (15:2008–2012.
    1. Tramacere I, Scotti L, Jenab M, Bagnardi V, Bellocco R, Rota M, Corrao G, Bravi F, Boffetta P, La Vecchia C. Alcohol drinking and pancreatic cancer risk: a meta-analysis of the dose-risk relation. Int J Cancer. 2010;126 (6:1474–1486.
    1. Tramacere I, Pelucchi C, Bagnardi V, Rota M, Scotti L, Islami F, Corrao G, Boffetta P, La Vecchia C, Negri E. A meta-analysis on alcohol drinking and esophageal and gastric cardia adenocarcinoma risk. Ann Oncol. 2012;23 (2:287–297.
    1. Tramacere I, Negri E, Pelucchi C, Bagnardi V, Rota M, Scotti L, Islami F, Corrao G, La Vecchia C, Boffetta P. A meta-analysis on alcohol drinking and gastric cancer risk. Ann Oncol. 2012;23 (1:28–36.
    1. Tramacere I, Pelucchi C, Bonifazi M, Bagnardi V, Rota M, Bellocco R, Scotti L, Islami F, Corrao G, Boffetta P, La Vecchia C, Negri E. A meta-analysis on alcohol drinking and the risk of Hodgkin lymphoma. Eur J Cancer Prev. 2012;21 (3:268–273.
    1. Tramacere I, Pelucchi C, Bonifazi M, Bagnardi V, Rota M, Bellocco R, Scotti L, Islami F, Corrao G, Boffetta P, La Vecchia C, Negri E. Alcohol drinking and non-Hodgkin lymphoma risk: a systematic review and a meta-analysis. Ann Oncol. 2012;23 (11:2791–2798.
    1. Trichopoulos D, Day NE, Kaklamani E, Tzonou A, Muñoz N, Zavitsanos X, Koumantaki Y, Trichopoulou A. Hepatitis B virus, tobacco smoking and ethanol consumption in the etiology of hepatocellular carcinoma. Int J Cancer. 1987;39 (1:45–49.
    1. Turati F, Gallus S, Tavani A, Tramacere I, Polesel J, Talamini R, Montella M, Scotti L, Franceshi S, La Vecchia C. Alcohol and endometrial cancer risk: a case-control study and a meta-analysis. Cancer Causes Control. 2010;21 (8:1285–1296.
    1. Turati F, Garavello W, Tramacere I, Bagnardi V, Rota M, Scotti L, Islami F, Corrao G, Boffetta P, La Vecchia C, Negri E. A meta-analysis of alcohol drinking and oral and pharyngeal cancers. Part 2: results by subsites. Oral Oncol. 2010;46 (10:720–726.
    1. Watson RR, Nixon P, Seitz HK, Maclennan R. Alcohol and cancer. Alcohol Alcohol Suppl. 1994;2:453–455.
    1. World Health Organization . Global Status Report on Alcohol and Health. World Health Organization: Geneva, Switzerland; 2011.
    1. Yu HS, Oyama T, Isse T, Kitagawa K, Pham TT, Tanaka M, Kawamoto T. Formation of acetaldehyde-derived DNA adducts due to alcohol exposure. Chem Biol Interact. 2010;188:367–375.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj