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.

Br J Cancer. 2011 Oct 25;105(9):1430-5. doi: 10.1038/bjc.2011.360. Epub 2011 Sep 13.
Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study.
Koh WP, Robien K, Wang R, Govindarajan S, Yuan JM, Yu MC.
Source
Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, MD3, Singapore 117597, Singapore. This e-mail address is being protected from spambots. You need JavaScript enabled to view it
Abstract
BACKGROUND:
Given the close correlation between smoking and alcohol intake in most epidemiologic studies, it is difficult to exclude the residual confounding effect of alcohol in the association between smoking and hepatocellular carcinoma (HCC).
METHOD:
We evaluated the association between smoking and risk of HCC in the Singapore Chinese Health Study, a prospective cohort with a low prevalence of alcohol intake. Information on cigarette smoking and alcohol consumption was obtained through in-person interviews conducted at enrolment.
RESULTS:
After a mean of 11.5 years of follow-up, there were 394 incident cases of HCC. Participants who consumed more than two alcoholic drinks per day showed an increased risk for HCC (hazard ratio (HR)=2.24; 95% confidence interval (CI)=1.46-3.41). After adjusting for alcohol consumption and other potential confounders, current vs never smokers had a statistically significant, increased risk of HCC (HR=1.63; 95% CI=1.27-2.10) that was dose-dependent (number of cigarettes per day, P for trend<0.001). The observed tobacco-HCC association also was duration-dependent (years of smoking in ever smokers, P for trend=0.002). When we excluded daily drinkers from the analysis, all risk estimates remained essentially the same and statistically significant.
CONCLUSION:
Our findings strongly implicate tobacco smoke as a causal factor of HCC development.