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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.

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 2107 controls 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.

journal_name

Eur J Clin Nutr

journal_title

European journal of clinical nutrition

authors

Ferrari P,McKay JD,Jenab M,Brennan P,Canzian F,Vogel U,Tjønneland A,Overvad K,Tolstrup JS,Boutron-Ruault MC,Clavel-Chapelon F,Morois S,Kaaks R,Boeing H,Bergmann M,Trichopoulou A,Katsoulis M,Trichopoulos D,Krogh V,Pa

doi

10.1038/ejcn.2012.173

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

1303-8

issue

eissn

0954-3007

issn

1476-5640

pii

ejcn2012173

journal_volume

pub_type

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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.