Alcohol & Alcoholism Vol. 39, No. 3, pp. 155-165, 2004
Alcohol & Alcoholism Vol. 39, No. 3 © Medical Council on Alcohol 2004; all rights reserved
REVIEW
ALCOHOL AND CANCER
Department of Medicine, Salem Medical Centre, Heidelberg and Laboratory of Alcohol Research, Liver Disease and Nutrition, Heidelberg, Germany
* Author to whom correspondence should be addressed at: Helmut K. Seitz MD, Department of Medicine, Salem Medical Centre, Zeppelinstrasse 11–33, D-69121 Heidelberg, Germany. Fax: +00 49 (0) 6221 483494; E-mail: helmut_karl.seitz{at}urz.uni-heidelberg.de
(Received 9 January 2004; first review notified 29 January 2004; in revised form 18 February 2004; accepted 18 February 2004)
Epidemiological data have identified chronic alcohol consumption as a significant risk factor for upper alimentary tract cancer, including cancer of the oropharynx, larynx and the oesophagus and of the liver. The increased risk attributable to alcohol consumption of cancer in the large intestine and in the breast is much smaller. However, although the risk is lower, carcinogenesis can be enhanced with relatively low daily doses of ethanol. Considering the high prevalence of these tumours, even a small increase in cancer risk is of great importance, especially in those individuals who exhibit a higher risk for other reasons. The epidemiological data on alcohol and other organ cancers is controversial and there is at present not enough evidence for a significant association. Although the exact mechanisms by which chronic alcohol ingestion stimulates carcinogenesis are not known, experimental studies in animals support the concept that ethanol is not a carcinogen but under certain experimental conditions is a cocarcinogen and/or tumour promoter. The metabolism of ethanol leads to the generation of acetaldehyde (AA) and free radicals. Evidence has accumulated that acetaldehyde is predominantly responsible for alcohol associated carcinogenesis. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and proteins, destructs folate and results in secondary hyperproliferation. Acetaldehyde is produced by tissue alcohol hydrogenases, cytochrome P 4502E1 and through bacterial oxidative metabolism in the upper and lower gastrointestinal tract. Its generation or its degradation is modulated due to functional polymorphisms of the genes coding for the enzymes. Acetaldehyde can also be produced by oral and faecal bacteria. Smoking, which changes the oral bacterial flora, and poor oral hygiene also increase acetaldehyde. In addition, cigarette smoking and some alcoholic beverages such as calvados contain acetaldehyde. Other mechanisms by which alcohol stimulates carcinogenesis include the induction of cytochrome P-4502E1, which is associated with an enhanced production of free radicals and enhanced activation of various procarcinogens present in alcoholic beverages; in association with tobacco smoke and in diets, a change in the metabolism and distribution of carcinogens; alterations in cell cycle behaviour such as cell cycle duration leading to hyperproliferation; nutritional deficiencies, such as methyl-, vitamin E-, folate-, pyridoxal phosphate-, zinc- and selenium deficiencies and alterations of the immune system eventually resulting in an increased susceptibility to certain virus infections such as hepatitis B virus and hepatitis C virus. In addition, local mechanisms may be of particular importance. Such mechanisms lead to tissue injury such as cirrhosis of the liver, a major prerequisite for hepatocellular carcinoma. Also, an alcohol-mediated increase in oestradiols may be at least in part responsible for breast cancer risk. Thus, all these mechanisms functioning in concert actively modulate carcinogenesis leading to its stimulation.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Bagnardi, G. Randi, J. Lubin, D. Consonni, T. K. Lam, A. F. Subar, A. M. Goldstein, S. Wacholder, A. W. Bergen, M. A. Tucker, et al. Alcohol Consumption and Lung Cancer Risk in the Environment and Genetics in Lung Cancer Etiology (EAGLE) Study Am. J. Epidemiol., November 22, 2009; (2009) kwp332v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. N. Garcia, O. A. Curioni, M. B. de Carvalho, and G. J. F. Gattas Polymorphisms in Alcohol Metabolizing Genes and the Risk of Head and Neck Cancer in a Brazilian Population Alcohol Alcohol., November 3, 2009; (2009) agp078v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Lubin, M. Purdue, K. Kelsey, Z.-F. Zhang, D. Winn, Q. Wei, R. Talamini, N. Szeszenia-Dabrowska, E. M. Sturgis, E. Smith, et al. Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer: A Pooled Analysis of Case-Control Studies Am. J. Epidemiol., October 15, 2009; 170(8): 937 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sun, I. R. Konig, and N. Homann Manganese Superoxide Dismutase (MnSOD) Polymorphism, Alcohol, Cigarette Smoking and Risk of Oesophageal Cancer Alcohol Alcohol., July 1, 2009; 44(4): 353 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Silberbogen, E. W. Ulloa, E. A. Janke, and D. L. Mori Psychosocial Issues and Mental Health Treatment Recommendations for Patients With Hepatitis C Psychosomatics, March 1, 2009; 50(2): 114 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Genkinger, D. Spiegelman, K. E. Anderson, L. Bergkvist, L. Bernstein, P. A. van den Brandt, D. R. English, J. L. Freudenheim, C. S. Fuchs, G. G. Giles, et al. Alcohol Intake and Pancreatic Cancer Risk: A Pooled Analysis of Fourteen Cohort Studies Cancer Epidemiol. Biomarkers Prev., March 1, 2009; 18(3): 765 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Frieden, J. E. Myers, M. S. Krauskopf, and T. A. Farley A Public Health Approach to Winning the War Against Cancer Oncologist, December 1, 2008; 13(12): 1306 - 1313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Kendzor, T. J. Costello, Y. Li, J. I. Vidrine, C. A. Mazas, L. R. Reitzel, P. M. Cinciripini, L. M. Cofta-Woerpel, M. S. Businelle, and D. W. Wetter Race/Ethnicity and Multiple Cancer Risk Factors among Individuals Seeking Smoking Cessation Treatment Cancer Epidemiol. Biomarkers Prev., November 1, 2008; 17(11): 2937 - 2945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Kendzor, L. M. Cofta-Woerpel, C. A. Mazas, Y. Li, J. I. Vidrine, L. R. Reitzel, T. J. Costello, M. S. Businelle, J. S. Ahluwalia, P. M. Cinciripini, et al. Socioeconomic Status, Negative Affect, and Modifiable Cancer Risk Factors in African-American Smokers Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2546 - 2554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Morrow, J. P. Cullen, P. A. Cahill, and E. M. Redmond Ethanol stimulates endothelial cell angiogenic activity via a Notch- and angiopoietin-1-dependent pathway Cardiovasc Res, July 15, 2008; 79(2): 313 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Thygesen, L. S. Morch, N. Keiding, C. Johansen, and M. Gronbaek Use of baseline and updated information on alcohol intake on risk for breast cancer: importance of latency Int. J. Epidemiol., June 1, 2008; 37(3): 669 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rohrmann, J. Linseisen, T. J. Key, M. K. Jensen, K. Overvad, N. F. Johnsen, A. Tjonneland, R. Kaaks, M. M. Bergmann, C. Weikert, et al. Alcohol Consumption and the Risk for Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1282 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Venkata, C. S. Aung, P. J. Cabot, G. R. Monteith, and S. J. Roberts-Thomson PPAR{alpha} and PPAR{beta} Are Differentially Affected by Ethanol and the Ethanol Metabolite Acetaldehyde in the MCF-7 Breast Cancer Cell Line Toxicol. Sci., March 1, 2008; 102(1): 120 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Suzuki, A. Seth, and R. Rao Role of Phospholipase C{gamma}-induced Activation of Protein Kinase C{epsilon} (PKC{epsilon}) and PKC{beta}I in Epidermal Growth Factor-mediated Protection of Tight Junctions from Acetaldehyde in Caco-2 Cell Monolayers J. Biol. Chem., February 8, 2008; 283(6): 3574 - 3583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Hsu, W.-H. Chow, P. Boffetta, L. Moore, D. Zaridze, A. Moukeria, V. Janout, H. Kollarova, V. Bencko, M. Navratilova, et al. Dietary Risk Factors for Kidney Cancer in Eastern and Central Europe Am. J. Epidemiol., July 1, 2007; 166(1): 62 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Strati, H. C. Pitot, and P. F. Lambert Identification of biomarkers that distinguish human papillomavirus (HPV)-positive versus HPV-negative head and neck cancers in a mouse model PNAS, September 19, 2006; 103(38): 14152 - 14157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Hooper, S. J. Crean, M. A. O. Lewis, D. A. Spratt, W. G. Wade, and M. J. Wilson Viable Bacteria Present within Oral Squamous Cell Carcinoma Tissue. J. Clin. Microbiol., May 1, 2006; 44(5): 1719 - 1725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wanibuchi, M. Wei, M. R. Karim, K. Morimura, K. Doi, A. Kinoshita, and S. Fukushima Existence of No Hepatocarcinogenic Effect Levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with or without Coadministration with Ethanol Toxicol Pathol, April 1, 2006; 34(3): 232 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. KIM and S. D. SHUKLA ACUTE IN VIVO EFFECT OF ETHANOL (BINGE DRINKING) ON HISTONE H3 MODIFICATIONS IN RAT TISSUES Alcohol Alcohol., March 1, 2006; 41(2): 126 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Travis, C. S. Rabkin, L. M. Brown, J. M. Allan, B. P. Alter, C. B. Ambrosone, C. B. Begg, N. Caporaso, S. Chanock, A. DeMichele, et al. Cancer Survivorship--Genetic Susceptibility and Second Primary Cancers: Research Strategies and Recommendations J Natl Cancer Inst, January 4, 2006; 98(1): 15 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. J. Salaspuro, J. M. Hietala, M. L. Marvola, and M. P. Salaspuro Eliminating Carcinogenic Acetaldehyde By Cysteine From Saliva During Smoking Cancer Epidemiol. Biomarkers Prev., January 1, 2006; 15(1): 146 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Baglietto, D. R English, D. M Gertig, J. L Hopper, and G. G Giles Does dietary folate intake modify effect of alcohol consumption on breast cancer risk? Prospective cohort study BMJ, October 8, 2005; 331(7520): 807. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Maggiolini, A G Recchia, D Bonofiglio, S Catalano, A Vivacqua, A Carpino, V Rago, R Rossi, and S Ando The red wine phenolics piceatannol and myricetin act as agonists for estrogen receptor {alpha} in human breast cancer cells J. Mol. Endocrinol., October 1, 2005; 35(2): 269 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Basuroy, P. Sheth, C. M. Mansbach, and R. K. Rao Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: protection by EGF and L-glutamine Am J Physiol Gastrointest Liver Physiol, August 1, 2005; 289(2): G367 - G375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Theruvathu, P. Jaruga, R. G. Nath, M. Dizdaroglu, and P. J. Brooks Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine adducts from acetaldehyde Nucleic Acids Res., June 21, 2005; 33(11): 3513 - 3520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. POLEDNAK RECENT TRENDS IN INCIDENCE RATES FOR SELECTED ALCOHOL-RELATED CANCERS IN THE UNITED STATES Alcohol Alcohol., May 1, 2005; 40(3): 234 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ziavrou, V. A. Boumba, and T. G. Vougiouklakis Insights into the Origin of Postmortem Ethanol International Journal of Toxicology, March 1, 2005; 24(2): 69 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Antony, J. A. Theruvathu, P. J. Brooks, D.-T. Lesher, M. Redinbo, and Y. Pommier Enhancement of camptothecin-induced topoisomerase I cleavage complexes by the acetaldehyde adduct N2-ethyl-2'-deoxyguanosine Nucleic Acids Res., October 21, 2004; 32(18): 5685 - 5692. [Abstract] [Full Text] [PDF]
|
|