Skip to main content
    • Aa
    • Aa
  • Access
  • Cited by 49
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Chen, Dong Gong, Liang Jiang, Qichuan Wang, Xuefeng and Zhang, Bin 2016. Interaction betweenMLL3genetic polymorphisms, smoking, and alcohol drinking in laryngeal cancer: a case-control study. Cancer Medicine, Vol. 5, Issue. 3, p. 527.

    Gonzales, Joseph F. Barnard, Neal D. Jenkins, David J.A. Lanou, Amy J. Davis, Brenda Saxe, Gordon and Levin, Susan 2014. Applying the Precautionary Principle to Nutrition and Cancer. Journal of the American College of Nutrition, Vol. 33, Issue. 3, p. 239.

    Novak Kujundžić, Renata Grbeša, Ivana Ivkić, Mirko Krušlin, Božo Konjevoda, Paško and Gall Trošelj, Koraljka 2014. Possible Prognostic Value of BORIS Transcript Variants Ratio in Laryngeal Squamous Cell Carcinomas – a Pilot Study. Pathology & Oncology Research, Vol. 20, Issue. 3, p. 687.

    Catazaro, Jonathan R. and Brecher, Arthur S. 2013. The influence of B-complex vitamins upon the prolongation of prothrombin time by acetaldehyde. Blood Coagulation & Fibrinolysis, Vol. 24, Issue. 5, p. 477.

    Kim, Sun Young Hong, Seok Woo Kim, Mi-Ok Kim, Hyun-Sik Jang, Jung Eun Leem, Jaechan Park, In-Sun Lee, Ki-Up and Koh, Eun Hee 2013. S-adenosyl methionine prevents endothelial dysfunction by inducing heme oxygenase-1 in vascular endothelial cells. Molecules and Cells, Vol. 36, Issue. 4, p. 376.

    Milne, Elizabeth Greenop, Kathryn R. Scott, Rodney J. de Klerk, Nicholas H. Bower, Carol Ashton, Lesley J. Heath, John A. and Armstrong, Bruce K. 2013. Parental alcohol consumption and risk of childhood acute lymphoblastic leukemia and brain tumors. Cancer Causes & Control, Vol. 24, Issue. 2, p. 391.

    Zavras, Athanasios I. Shanmugam, Priyaa Shetty, Deepthi Dolecek, Therese A. and Kaste, Linda M. 2013. Oral and Pharyngeal Cancer in Women. Dental Clinics of North America, Vol. 57, Issue. 2, p. 339.

    Zempleni, Janos Cordonier, Elizabeth Baier, Scott and Xue, Jing 2013. Handbook of Vitamins, Fifth Edition.

    Christophersen, Olav Albert 2012. Should autism be considered a canary bird telling thatHomo sapiensmay be on its way to extinction?. Microbial Ecology in Health & Disease, Vol. 23,

    Gay, Laura J Mitrou, Panagiota N Keen, Jennifer Bowman, Richard Naguib, Adam Cooke, James Kuhnle, Gunter G Burns, Philip A Luben, Robert Lentjes, Marleen Khaw, Kay-Tee Ball, Richard Y Ibrahim, Ashraf EK and Arends, Mark J 2012. Dietary, lifestyle and clinicopathological factors associated withAPCmutations and promoter methylation in colorectal cancers from the EPIC-Norfolk study. The Journal of Pathology, Vol. 228, Issue. 3, p. 405.

    Moody, Michael Le, Oanh Rickert, Megan Manuele, Jeremy Chang, Sarah Robinson, Gary Hajibandeh, Jeffrey Silvaroli, John Keiserman, Mark A Bergman, Christine J and Kingsley, Karl 2012. Folic acid supplementation increases survival and modulates high risk HPV-induced phenotypes in oral squamous cell carcinoma cells and correlates with p53 mRNA transcriptional down-regulation. Cancer Cell International, Vol. 12, Issue. 1, p. 10.

    Howie, Erin K. Sui, Xuemei Lee, Duck-chul Hooker, Steven P. Hébert, James R. and Blair, Steven N. 2011. Alcohol Consumption and Risk of All-Cause and Cardiovascular Disease Mortality in Men. Journal of Aging Research, Vol. 2011, p. 1.

    Beasley, Jeannette M. Coronado, Gloria D. Livaudais, Jennifer Angeles-Llerenas, Angélica Ortega-Olvera, Carolina Romieu, Isabelle Lazcano-Ponce, Eduardo and Torres-Mejía, Gabriela 2010. Alcohol and risk of breast cancer in Mexican women. Cancer Causes & Control, Vol. 21, Issue. 6, p. 863.

    Chango, A. 2010. Les folates dans la prévention et dans le déterminisme du cancer. Journal Africain du Cancer / African Journal of Cancer, Vol. 2, Issue. 3, p. 171.

    Goldman-Mellor, Sidra J. Saxton, Katherine B. and Catalano, Ralph C. 2010. Economic Contraction and Mental Health. International Journal of Mental Health, Vol. 39, Issue. 2, p. 6.

    Kim, Mi Kyung Ko, Min Jung and Han, Jun Tae 2010. Alcohol consumption and mortality from all-cause and cancers among 1.34 million Koreans: the results from the Korea national health insurance corporation’s health examinee cohort in 2000. Cancer Causes & Control, Vol. 21, Issue. 12, p. 2295.

    Kingsley, Karl 2010. Potential Effects of Dietary Folate Supplementation on Oral Carcinogenesis, Development and Progression. Journal of Dietary Supplements, Vol. 7, Issue. 1, p. 51.

    Liu, Jia (Jenny) and Ward, Robyn Lynne 2010. Epigenetics and Cancer, Part B.

    Park, J. Y. Mitrou, P. N. Keen, J. Dahm, C. C. Gay, L. J. Luben, R. N. McTaggart, A. Khaw, K.-T. Ball, R. Y. Arends, M. J. and Rodwell, S. A. 2010. Lifestyle factors and p53 mutation patterns in colorectal cancer patients in the EPIC-Norfolk study. Mutagenesis, Vol. 25, Issue. 4, p. 351.

    2010. Handbook of Alcoholic Beverages.


Alcohol and cancer: genetic and nutritional aspects

  • Gudrun Pöschl (a1), Felix Stickel (a2), Xiang D. Wang (a3) and Helmut K. Seitz (a1)
  • DOI:
  • Published online: 01 March 2007

Chronic alcohol consumption is a major risk factor for cancer of upper aero-digestive tract (oro-pharynx, hypopharynx, larynx and oesophagus), the liver, the colo-rectum and the breast. Evidence has accumulated that acetaldehyde is predominantly responsible for alcohol-associated carcinogenesis. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and protein, destroys the folate molecule and results in secondary cellular hyper-regeneration. Acetaldehyde is produced by mucosal and cellular alcohol dehydrogenase, cytochrome P450 2E1 and through bacterial oxidation. Its generation and/or its metabolism is modulated as a result of polymorphisms or mutations of the genes responsible for these enzymes. Acetaldehyde can also be produced by oral bacteria. Smoking, which changes the oral bacterial flora, also increases salivary acetaldehyde. Cigarette smoke and some alcoholic beverages, such as Calvados, contain acetaldehyde. In addition, chronic alcohol consumption induces cytochrome P450 2E1 enxyme activity in mucosal cells, resulting in an increased generation of reactive oxygen species and in an increased activation of various dietary and environmental carcinogens. Deficiencies of riboflavin, Zn, folate and possibly retinoic acid may further enhance alcohol-associated carcinogenesis. Finally, methyl deficiency as a result of multiple alcohol-induced changes leads to DNA hypomethylation. A depletion of lipotropes, including methionine, choline, betaine and S-adenosylmethionine, as well as folate, results in the hypomethylation of oncogenes and may lead to DNA strand breaks, all of which are associated with increased carcinogenesis.

    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Alcohol and cancer: genetic and nutritional aspects
      Your Kindle email address
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Alcohol and cancer: genetic and nutritional aspects
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Alcohol and cancer: genetic and nutritional aspects
      Available formats
Corresponding author
*Corresponding author: Professor Helmut K. Seitz, fax + 49 6221 483494, email
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

AJ Barak , HC Beckenhauer , N Hidiroglou , ME Camilo , J Selhub & DJ Tuma (1993) The relationship of ethanol feeding to the methyl folate trap. Alcohol 10, 495497.

JL Counts & JI Goodman (1995) Alterations in DNA methylation play a variety of roles in carcinogenesis. Cell 83, 1315.

DW Crabb , J Pinairs , R Hasanadka , M Fang , MA Leo , CS Lieber , et al. (2001) Alcohol and retinoids. Alcohol, Clinical and Experimental Research 25, 207S217S.

Z Gouillon , D Lucas , J Li , AL Hagbjork , BA French , P Fu , C Fang , M Ingelman-Sundberg , TM Donohue Jr & SW French (2000) Inhibition of ethanol-induced liver disease in the intragastric feeding rat model by chlormethiazole. Proceedings of the Society for Experimental Biology and Medicine 224, 302308.

LC Harty , NE Caporaso , RB Hayes , DM Winn , E Bravo-Otero , WJ Blot , DV Kleinman , LM Brown , HK Armenian , JF Fraumeni Jr & PG Shields (1997) Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal cancers. Journal of the National Cancer Institute 89, 16981705.

N Homann , H Jousimies-Somer , K Jokelainen , R Heine & M Salaspuro (1997a) High acetaldehyde levels in saliva after ethanol consumption: Methodological aspects and pathogenetic implications. Carcinogenesis 18, 17391743.

N Homann , J Tillonen , H Rintamaki , M Salaspuro , C Lindqvist & JH Meurman (2001) Poor dental status increases the acetaldehyde production from ethanol in saliva. A possible link to the higher risk of oral cancer among alcohol consumers. Oral Oncology 37, 153158.

N Iwata , H Yamamoto , S Sasaki , F Itoh , H Suzuki , T Kikuchi et al. (2000) Frequent hypermethylation of CpG islands and loss of expression of the 14–3-3 sigma gene in human hepatocellular carcinoma. Oncogene 19, 52985302.

Y Kanai , AM Hui , L Sun , S Ushijima , M Sakamoto , H Tsuda & S Hirohashi (1999) DNA hypermethylation at the D17S5 locus and reduced HIC-1 mRNA expression are associated with hepatocarcinogenesis. Hepatology 29, 703709.

D Labadarios , JE Rossouw JB McConnell M Davis & R Williams (1977) Vitamin B6 deficiency in chronic liver disease – evidence for increased degradation of pyridoxal-5'-phosphate. Gut 18, 2327.

MA Leo & CS Lieber (1982) Hepatic vitamin A depletion in alcoholic liver injury. New England Journal of Medicine 307, 597601.

JJ Li , M Benesova , K Goette , W Fiehn , C Conradt , K Hoermann , M Salaspuro & HK Seitz (2001) Enhanced risk of upper alimentary tract cancer in patients with the alcohol dehydrogenase 3*1 allele due to increased salivary acetaldehyde following ethanol ingestion. Gastroenterology 120 A-160.

CS Lieber (1994b) Alcohol and the liver: 1994 update. Gastroenterology 106, 10851105.

CS Lieber , A Casini LM DeCarli CI Kim , N Lowe , R Sasaki & MA Leo (1990) S -adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatology 11, 165172.

C Liu , J Chung , HK Seitz , RM Russell & XD Wang (2002) Chlormethiazole treatment prevents reduced hepatic vitamin A levels in alcohol-fed rats. Alcohol, Clinical and Experimental Research 26, 17031709.

L Lumeng & TK Li (1974) Vitamin B6 metabolism in chronic alcohol abuse. Journal of Clinical Investigations 53, 693704.

T Matsuda , I Terashima , Y Matsumoto , H Yabushita , S Matsui & S Shibutani (1999) Effective utilization of N2-ethyl-2'-deoxyguanosine triphosphate during DNA synthesis catalyzed by mammalian replicative DNA polymerases. Biochemistry 38, 929935.

H Miyakawa , J Liu , O Noguchi , F Marumo & C Sato (1996) Effect of alcohol drinking on gene expression of hepatic O 6 -methylguanine DNA methyltransferase in chronic liver diseases. Alcohol, Clinical and Experimental Research 20, 297A300A.

AF Olshan , MC Weissler , MA Watson & DA Bell (2001) Risk of head and neck cancer and the alcohol dehydrogenase 3 genotype. Carcinogenesis 22, 5761.

M Sato & CS Lieber (1982) Increased metabolism of retinoic acid after chronic ethanol consumption in rat liver microsomes. Archives of Biochemistry and Biophysics 213, 557564.

HK Seitz , S Matsuzaki , A Yokoyama , N Homann , S Vakevainen & XD Wang (2001) Alcohol and cancer. Alcohol, Clinical and Experimental Research 25, 137143.

M Shimizu , JM Lasker , M Tsutsumi & CS Lieber (1990) Immunohistochemical localization of ethanol-inducible P450 2E1 in the rat alimentary tract. Gastroenterology 99, 10441053.

H Speisky A MacDonald G Giles , H Orrego & Y Israel (1985) Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Turnover studies. Biochemical Journal 225, 565572.

S Vakevainen , J Tillonen , DP Agarwal , N Srivastava & M Salaspuro (2000) High salivary acetaldehyde after a moderate dose of alcohol in ALDH2-deficient subjects: strong evidence for the local carcinogenic action of acetaldehyde. Alcohol, Clinical and Experimental Research 24, 873877.

XD Wang (2001) Retinoids and alcoholic liver disease Alcohol in Health and Disease 427452DP Agarwal , HK Seitz , New York: Marcel Dekker.

XD Wang , C Liu , J Chung , F Stickel , HK Seitz & RM Russell (1998) Chronic alcohol intake reduces retinoic acid concentration and enhances AP-1 (c-JUN and c-FOS) expression in rat liver. Hepatology 28, 744750.

A Yokoyama , T Muramatsu , T Ohmori , H Makuuchi , S Higuchi , S Matsushita , K Yoshino , K Maruyama , M Nakano & H Ishii (1996) Multiple primary esophageal and concurrent aerodigestive tract cancer and the aldehyde dehydrogenase-2 genotype of Japanese alcoholics. Cancer 77, 19861990.

A Yokoyama , T Muramatsu & T Ohmori (1998) Alcohol related cancers and aldehyde dehydrogenase in Japanese alcoholics. Carcinogenesis 19, 13831387.

MR Young , JJ Li , M Rincon , RA Flavell , BK Sathyanarayana , R Hunziker & N Colburn (1999) Transgenic mice demonstrate AP-1 (activator protein 1) transactivation is required for tumor promotion. Proceedings of the National Academy of Sciences USA 96, 98279832.

WF Zapisek & GM Cronin BD Lyn-Cook LA Poirier (1992) The onset of oncogene hypomethylation in the livers of rats fed methyl-deficient, amino acid-defined diets. Carcinogenesis 13, 18691872.

E Borras , C Coutelle , A Rosell , F Fernandez-Muixi , M Broch , B Crosas et al. (2000) Genetic polymorphism of alcohol dehydrogenase in Europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1 Hepatology 31, 984989.

J Chung , PR Chavez , RM Russell & XD Wang (2002) Retinoic acid inhibits hepatic Jun N-terminal kinase-dependent signaling pathway in ethanol-fed rats Oncogene 21, 15391547.

J Chung , C Liu , DE Smith , HK Seitz , RM Russell & XD Wang (2001) Restoration of retinoic acid concentration suppresses ethanol-enhanced c-Jun expression and hepatocyte proliferation in rat liver. Carcinogenesis 22, 12131219.

C Coutelle , PJ Ward , B Fleury , P Quattrocchi , H Chambrin , A Iron , P Couzigou & A Cassaigne (1997) Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms. Human Genetics 99, 319325.

VL Dellarco (1988) A mutagenicity assessment of acetaldehyde. Mutation Research 195, 120.

N Espina , V Lima , CS Lieber & AJ Garro (1988) In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O 6 -methylguanine transferase. Carcinogenesis 9, 761766.

JL Fang & CE Vaca (1995) Development of a 32P-postlabeling method for the analysis of adducts arising through the reaction of acetaldehyde with 2'-deoxyguanosine-3'-monophosphate and DNA. Carcinogenesis 16, 21772185.

JL Fang & CE Vaca (1997) Detection of DNA adducts of acetaldehyde in peripheral white blood cells of alcohol abusers. Carcinogenesis 18, 627632.

AJ Garro DL McBeth V Lima , CS Lieber (1991) Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol, Clinical and Experimental Research 15, 395398.

MA Grummer & RD Zachman (2000) Interaction of ethanol with retinol and retinoic acid in RAR beta and GAP-43 expression. Neurotoxicology and Teratology 22, 829836.

CH Halsted , J Villanueva , CJ Chandler , SP Stabler , RH Allen , L Muskhelishvili , SJ James & L Poirier (1996) Ethanol feeding of micropigs alters methionine metabolism and increases hepatocellular apoptosis and proliferation. Hepatology 23, 497505.

A Helander & K Lindahl-Kiessling (1991) Increased frequency of acetaldehyde-induced sister-chromatide exchanges in human lymphocytes treated with an aldehyde dehydrogenase inhibitor. Mutatation Research 264, 103107.

N Homann , P Karkkainen , T Koivisto , T Nosova , K Jokelainen & M Salaspuro (1997b) Effects of acetaldehyde on cell regeneration and differentiation of the upper gastrointestinal tract mucosa. Journal of the National Cancer Institute 89, 16921697.

N Homann , J Tillonen , JH Meurman , H Rintamaki , C Lindqvist , M Rautio , H Jousimies-Somer & M Salaspuro (2000) Increased salivary acetaldehyde levels in heavy drinkers and smokers: A microbiological approach to oral cavity cancer. Carcinogenesis 21, 663668.

K Jokelainen , E Heikkonen , R Roine , H Lehtonen & M Salaspuro (1996) Increased acetaldehyde production by mouthwashings from patients with oral cavity, laryngeal, or pharyngeal cancer. Alcohol, Clinical and Experimental Research 20, 12061210.

Y Kanai , S Ushijima , H Tsuda , M Sakamoto & S Hirohashi (2000) Aberrant DNA methylation precedes loss of heterozygosity on chromosome 16 in chronic hepatitis and liver cirrhosis. Cancer Letters 148, 7380.

MA Leo , C Kim & CS Lieber (1986) Increased vitamin A in esophagus and other extrahepatic tissues after chronic ethanol consumption in the rat. Alcohol, Clinical and Experimental Research 10, 487492.

CS Lieber (1994a) Mechanisms of ethanol-drug nutrition interactions. Journal of Toxicology Clinical Toxicology 32, 631681.

C Liu , RM Russell , HK Seitz & XD Wang (2001) Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P450 2E1. Gastroenterology 120, 179189.

H Maier , IA Born , S Veith , D Adler & HK Seitz (1986) The effect of chronic ethanol consumption on salivary gland morphology and function in the rat. Alcohol, Clinical and Experimental Research 10, 425427.

CM Oneta , CS Lieber , J Li , S Ruttimann , B Schmid , J Lattmann , AS Rosman & HK Seitz (2002) Dynamics of cytochrome P450 2E1 activity in man: induction by ethanol and disappearance during withdrawal phase. Journal of Hepatology 36, 4752.

MP Salaspuro (2003) Acetaldehyde, microbes, and cancer of the digestive tract. Critical Reviews in Clinical Laboratory Science 40, 183208.

HK Seitz & CM Oneta (1998) Gastrointestinal alcohol dehydrogenases. Nutrition Reviews 56, 5260.

UA Simanowski , P Suter , F Stickel , H Maier , R Waldherr , D Smith , RM Russell & HK Seitz (1993) Esophageal epithelial hyperregeneration following chronic ethanol ingestion: Effect of age and salivary gland function. Journal of the National Cancer Institute 85, 20302033.

D Simoni , M Tolomeo (2001) Retinoids, apoptosis and cancer. Current Pharmaceutical Design 7, 18231837.

F Stickel , SW Choi , YI Kim , PJ Bagley , HK Seitz , RM Russell , J Selhub & JB Mason (2000) Effect of chronic alcohol consumption on total plasma homocysteine level in rats. Alcohol, Clinical and Experimental Research 24, 259264.

F Stickel , N Homann , M Benesova , A Jacobs , D Schuppan , EG Hahn , C Conradt , D Ludwig , I Zuber , HE Blum & HK Seitz (2003) Genetic predisposition for alcohol associated upper aerodigestive tract cancer and hepatocellular cancer in heavy drinkers with the alcohol dehydrogenase 3*1 allele. Gastroenterology 124 A547

KC Trimble , AM Molloy , JM Scott & DG Weir (1993) The effect of ethanol on one-carbon metabolism: increased methionine catabolism and lipotrope methyl-group wastage. Hepatology 18, 984989.

RA Woutersen , LM Appelman , A Van Garderen-Hoetmer & VJ Feron (1986) Inhalation toxicity of acetaldehyde in rats: III. Carcinogenicity study. Toxicology 41, 213231.

A Yokoyama , T Muramatsu , T Omori , S Matsushita , H Yoshimizu , S Higuchi , T Yokoyama , K Maruyama & H Ishii (1999) Alcohol and aldehyde gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics. Alcohol, Clinical and Experimental Research 23, 17051710.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *