Impact of Alcohol Consumption on Gastric Cancer by ALDH allele PDF Print E-mail

Carcinogenesis. 2011 Dec 5. [Epub ahead of print]
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.
Duell EJ, Sala N, Travier N, Muñoz X, Boutron-Ruault MC, Clavel-Chapelon F, Barricarte A, Arriola L, Navarro C, Sánchez-Cantalejo E, Quirós JR, Krogh V, Vineis P, Mattiello A, Tumino R, Khaw KT, Wareham N, Allen NE, Peeters PH, Numans ME, Bueno-de-Mesquita HB, van Oijen MG, Bamia C, Benetou V, Trichopoulos D, Canzian F, Kaaks R, Boeing H, Bergmann MM, Lund E, Ehrnström R, Johansen D, Hallmans G, Stenling R, Tjønneland A, Overvad K, Ostergaard JN, Ferrari P, Fedirko V, Jenab M, Nesi G, Riboli E, González CA.
Source
Unit of Nutrition, Environment and Cancer, Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
Abstract
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 (ADH1 gene cluster: ADH1A, ADH1B, and ADH1C; ADH7; and ALDH2), alcohol intake, and GC risk. We analysed data from a nested case-control study (364 cases and 1272 controls) within the EPIC cohort. Single nucleotide polymorphisms (SNP) 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 OR(A v T)=1.30, 95% 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 grams per day: OR(A)=0.89, 95% CI=0.57-1.39; ≥5 grams per 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.

 

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