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Nutrigenomics and molecular nutrition

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 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) (Pdiff<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 (Pinteraction=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.

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Acknowledgements

The EPIC study was funded by the ‘Europe Against Cancer’ Programme of the European Commission (SANCO); the Ligue contre le Cancer (France); the Société 3 M (France); the Mutuelle Générale de l’Education Nationale; the Institut National de la Santé et de la Recherche Médicale (INSERM); the German Cancer Aid; the German Cancer Research Center; the German Federal Ministry of Education and Research; the Danish Cancer Society; the Health Research Fund (FIS) of the Spanish Ministry of Health (RETIC-RD06/0020); the participating regional governments and institutions of Spain; The ISCIII Red de Centro RCESP (C03/09); the Cancer Research, UK; the Medical Research Council, UK; the Stroke Association, UK; the British Heart Foundation; the Department of Health, UK; the Food Standards Agency, UK; the Wellcome Trust, UK; the Greek Ministry of Health and Social Solidarity; the Hellenic Health Foundation and Stavros Niarchos Foundation; the Italian Association for Research on Cancer; the Italian National Research Council; the Compagnia di San Paolo; the Dutch Ministry of Public Health, Welfare and Sports; the Dutch Ministry of Health; the Dutch Prevention Funds; the LK Research Funds; the Dutch ZON (Zorg Onderzoek Nederland); the World Cancer Research Fund; the Swedish Cancer Society; the Swedish Scientific Council; the Regional Government of Skane, Sweden and the Norwegian Cancer Society.

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Correspondence to P Ferrari.

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Ferrari, P., McKay, J., Jenab, M. et al. 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. Eur J Clin Nutr 66, 1303–1308 (2012). https://doi.org/10.1038/ejcn.2012.173

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