Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma

Abstract

The effect of genetic polymorphisms for glutathione S-transferase (GST) M1, GSTT1, GSTP1-1 (GSTP1), cytochrome P450 2E 1 (CYP2E1) and aldehyde dehydrogenase 2 (ALDH2) on the risk of hepatocellular carcinoma (HCC) was observed in 78 Japanese patients with HCC and 138 non-cancer hospital controls. We found a positive association between cumulative amounts of alcohol consumption (≧600,000 ml in a lifetime) and the risk of HCC (OR=4.52, 95% CI 2.39-8.55). However, cigarette smoking was not significantly related to the risk of HCC (OR = 1.23; 95% CI 0.57-2.68). The allelic frequencies of GSTM1, GSTT1, GSTP1, CYP2E1 and ALDH2 of HCC patients were not significantly different from those of controls when odds ratios were only adjusted for age and gender except for any 2 alleles of ALDH2 in drinkers (OR=2.53, 95% CI 1.21-5.31). However, the frequency of any C2alleles of CYP2E1 and any 2 alleles of ALDH2 were significantly higher than those of controls (OR=5.77, 95% CI 1.24-27.39, OR = 9.77, 95% CI 1.63-58.60) when covariates including viremia were selected by using stepwise logistic regression analysis. We conclude that habitual alcohol drinking is likely to lead to an increased risk of HCC, and any C2 alleles of CYP2E1 as well as any two alleles of ALDH2 were also associated with an increased risk of HCC.