Alcohol dehydrogenase 3, glutathione S-transferase M1 and T1 polymorphisms, alcohol consumption and hepatocellular carcinoma (Italy)

Objective: The aim of this study was to investigate the role of alcohol dehydrogenase type 3 (ADH3), glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms in modifying hepatocellular carcinoma (HCC) risk according to alcohol intake. Methods: A hospital-based case-control study was conducted in two areas of North Italy. Two-hundred cases hospitalized for HCC and 400 controls were recruited. Genotypes were determined using PCR and the PCR/restriction fragment length polymorphism-based method. Results: There was no association of the putative risk genotypes ADH3^1-1, GSTM1 null and GSTT1 null with HCC (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.5-1.3; OR, 1.0; 95% CI, 0.6-1.5; OR, 0.8; 95% CI, 0.4-1.4, respectively). A steady increase in HCC risk with increasing alcohol intake, which did not vary according to ADH3 and GSTT1 genotypes, was observed. Nevertheless, the OR for HCC due to an alcohol intake of >100 g of ethanol per day increased in subjects with GSTM1 null genotype (OR, 8.5; 95% CI, 3.9-18.6) compared to GSTM1 non-null genotype (OR, 4.5; 95% CI, 2.0-10.0). Conclusions: ADH3^1-1 and GSTT1 null genotypes did not modify the risk of HCC due to alcohol intake whereas an influence of GSTM1 null genotype for high ethanol consumption was suggested.