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Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

Title
Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study
Publication type
Journal Article
Year of Publication
2012
Authors
Ferrari, P., McKay, J.D., Jenab, M., Brennan, P., Canzian, F., Vogel, U., Tjonneland, A., Overvad, K., Tolstrup, J.S., Boutron-Ruault, M.-C., Clavel-Chapelon, F., Morois, S., Kaaks, R., Boeing, H., Bergmann, M., Trichopoulou, A., Katsoulis, M., Trichopoulos, D., Krogh, V., Panico, S., Sacerdote, C., Palli, D., Tumino, R., Peeters, P.H., van Gils, C.H., Bueno-De-Mesquita, B., Vrieling, A., Lund, E., Hjartåker, A., Agudo, A., Suarez, L.R., Arriola, L., Chirlaque, M.-D., Ardanaz, E., Sánchez, M.-J., Manjer, J., Lindkvist, B., Hallmans, G., Palmqvist, R., Allen, N., Key, T., Khaw, K.-T., Slimani, N., Rinaldi, S., Romieu, I., Boffetta, P., Romaguera, D., Norat, T., Riboli, E.
Journal
European Journal of Clinical Nutrition
Volume
66
Issue
12
Pagination
1303 - 1308
Date published
2012
ISBN
09543007 (ISSN)
Keywords
acetaldehyde, Adult, Aged, alcohol consumption, alcohol dehydrogenase, alcohol dehydrogenase 1b, alcohol dehydrogenase 1b gene, alcohol dehydrogenase 7, alcohol dehydrogenase 7 gene, Alcohol Drinking, Alcohol intake, Aldehyde Dehydrogenase, aldehyde dehydrogenase 2 gene, aldehyde dehydrogenase isoenzyme 2, allele, Alleles, article, beer, blood sampling, cancer risk, case control study, Case-Control Studies, Caucasian, cohort analysis, colorectal cancer, Colorectal Neoplasms, confidence interval, controlled study, Denmark, drinking behavior, Ethanol, Europe, European Continental Ancestry Group, Female, folic acid, France, Germany, Greece, human, Netherlands, Norway, Odds Ratio, Polymorphism, Polymorphism, Genetic, Prospective Studies, risk assessment, Risk Factors, single nucleotide polymorphism, Spain, Sweden, unclassified drug, United Kingdom, wild type, wine
Abstract

Background/objectives:Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations.Subjects/methods:A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors.Results:Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P diff <0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption (P interaction =0.07).Conclusions:The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism.

DOI
https://dx.doi.org/10.1038/ejcn.2012.173
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