Plasma Carotenoids, Glutathione S-Transferase M1 andT1 Genetic Polymorphisms, and Risk of Hepatocellular Carcinoma: Independent and Interactive Effects

Abstract

This study was conducted to assess the role of carotenoid and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in the development of hepatocellular carcinoma (HCC). A total of 84 incident cases of HCC and 375 matched controls selected from a cohort of 7,342 men (4,841 chronic hepatitis B carriers and 2,501 noncarriers) who were recruited between 1988 and 1992 in Taiwan were studied. Neither GST M1/T1 polymorphisms nor plasma levels of various carotenoids were independently associated with HCC, but they modulated smoking- and/or drinking-related HCC risk. Cumulative exposure to tobacco smoke significantly increased HCC risk in a dose-dependent manner among subjects with low plasma β-carotene levels (p for trend = 0.047) but not among those with high levels. A statistically significant effect of habitual alcohol drinking on HCC risk was observed only for those with low plasma levels of β-carotene, α-carotene, or lycopene and for GST M1 null subjects. There was evidence suggesting an interaction between the GST M1/T1 genotype and certain carotenoids in HCC associated with smoking and drinking. The strongest effect of smoking and drinking was noted among GST M1 null subjects with low plasma levels of β-carotene (smoking: adjusted odds ratio (OR) = 3.54, 95% confidence interval (Cl) 1.06–11.83; drinking: OR = 8.28, 95% Cl 2.40–28.61). Am J Epidemiol 1999; 149: 621–9.