Document Detail

Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
MedLine Citation:
PMID:  22144473     Owner:  NLM     Status:  MEDLINE    
Studies that have examined the association between alcohol consumption and gastric cancer (GC) risk have been inconsistent. We conducted an investigation of 29 genetic variants in alcohol metabolism loci (alcohol dehydrogenase, ADH1 gene cluster: ADH1A, ADH1B and ADH1C; ADH7 and aldehyde dehydrogenase, ALDH2), alcohol intake and GC risk. We analyzed data from a nested case-control study (364 cases and 1272 controls) within the European Prospective Investigation into Cancer and Nutrition cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. We observed a statistically significant association between a common 3'-flanking SNP near ADH1A (rs1230025) and GC risk [allelic odds ratio (OR)(A v T) = 1.30, 95% confidence interval (CI) = 1.07-1.59]. Two intronic variants, one in ADH1C (rs283411) and one in ALDH2 (rs16941667), also were associated with GC risk (OR(T v C) = 0.59; 95% CI = 0.38-0.91 and OR(T v C) = 1.34; 95% CI = 1.00-1.79, respectively). Individuals carrying variant alleles at both ADH1 (rs1230025) and ALDH2 (rs16941667) were twice as likely to develop GC (OR(A+T) = 2.0; 95% CI = 1.25-3.20) as those not carrying variant alleles. The association between rs1230025 and GC was modified by alcohol intake (<5 g/day: OR(A) = 0.89, 95% CI = 0.57-1.39; ≥5 g/day: OR(A) = 1.45, 95% CI = 1.08-1.94, P-value = 0.05). The association was also modified by ethanol intake from beer. A known functional SNP in ADH1B (rs1229984) was associated with alcohol intake (P-value = 0.04) but not GC risk. Variants in ADH7 were not associated with alcohol intake or GC risk. In conclusion, genetic variants at ADH1 and ALDH2 loci may influence GC risk, and alcohol intake may further modify the effect of ADH1 rs1230025. Additional population-based studies are needed to confirm our results.
Eric J Duell; Núria Sala; Noémie Travier; Xavier Muñoz; Marie Christine Boutron-Ruault; Françoise Clavel-Chapelon; Aurelio Barricarte; Larraitz Arriola; Carmen Navarro; Emilio Sánchez-Cantalejo; J Ramón Quirós; Vittorio Krogh; Paolo Vineis; Amalia Mattiello; Rosario Tumino; Kay-Tee Khaw; Nicholas Wareham; Naomi E Allen; Petra H Peeters; Mattijs E Numans; H B Bueno-de-Mesquita; M G H van Oijen; Christina Bamia; Vassiliki Benetou; Dimitrios Trichopoulos; Federico Canzian; Rudolf Kaaks; Heiner Boeing; Manuela M Bergmann; Eiliv Lund; Roy Ehrnström; Dorthe Johansen; Göran Hallmans; Roger Stenling; Anne Tjønneland; Kim Overvad; Jane Nautrup Ostergaard; Pietro Ferrari; Veronika Fedirko; Mazda Jenab; Gabriella Nesi; Elio Riboli; Carlos A González
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-12-05
Journal Detail:
Title:  Carcinogenesis     Volume:  33     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-06     Completed Date:  2012-06-12     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  361-7     Citation Subset:  IM    
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MeSH Terms
Alcohol Dehydrogenase / genetics*
Alcohol Drinking / genetics*,  metabolism
Alcoholism / enzymology,  genetics
Aldehyde Dehydrogenase / genetics*
Case-Control Studies
Cohort Studies
European Continental Ancestry Group / genetics*
Follow-Up Studies
Genetic Loci
Haplotypes / genetics
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide
Prospective Studies
Risk Factors
Stomach Neoplasms / enzymology,  etiology,  genetics*
Grant Support
11692//Cancer Research UK; G0401527//Medical Research Council; G1000143//Medical Research Council; MC_U106179471//Medical Research Council; //Cancer Research UK; //Medical Research Council
Reg. No./Substance:
0/Isoenzymes; EC Dehydrogenase; EC Dehydrogenase

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