Document Detail


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.
MedLine Citation:
PMID:  23149980     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
P Ferrari; J D McKay; M Jenab; P Brennan; F Canzian; U Vogel; A Tjønneland; K Overvad; J S Tolstrup; M-C Boutron-Ruault; F Clavel-Chapelon; S Morois; R Kaaks; H Boeing; M Bergmann; A Trichopoulou; M Katsoulis; D Trichopoulos; V Krogh; S Panico; C Sacerdote; D Palli; R Tumino; P H Peeters; C H van Gils; B Bueno-de-Mesquita; A Vrieling; E Lund; A Hjartåker; A Agudo; L R Suarez; L Arriola; M-D Chirlaque; E Ardanaz; M-J Sánchez; J Manjer; B Lindkvist; G Hallmans; R Palmqvist; N Allen; T Key; K-T Khaw; N Slimani; S Rinaldi; I Romieu; P Boffetta; D Romaguera; T Norat; E Riboli
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  European journal of clinical nutrition     Volume:  66     ISSN:  1476-5640     ISO Abbreviation:  Eur J Clin Nutr     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-05     Completed Date:  2013-05-10     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8804070     Medline TA:  Eur J Clin Nutr     Country:  England    
Other Details:
Languages:  eng     Pagination:  1303-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aged
Alcohol Dehydrogenase / genetics*
Alcohol Drinking / genetics*,  metabolism
Aldehyde Dehydrogenase / genetics*
Alleles
Case-Control Studies
Colorectal Neoplasms / genetics*
Ethanol / metabolism*
Europe
European Continental Ancestry Group / genetics*
Female
Humans
Logistic Models
Male
Middle Aged
Odds Ratio
Polymorphism, Genetic*
Prospective Studies
Risk Assessment
Risk Factors
Grant Support
ID/Acronym/Agency:
11692//Cancer Research UK; G1000143//Medical Research Council; //British Heart Foundation; //Cancer Research UK; //Department of Health; //Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
3K9958V90M/Ethanol; EC 1.1.1.1/Alcohol Dehydrogenase; EC 1.2.1.3/Aldehyde Dehydrogenase

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