Plasma carotenoids, glutathione S-Transferase M1 and T1 genetic polymorphisms, and risk of hepatocellular carcinoma: Independent and interactive effects

This study was conducted to assess the role of carotenoid and glutathione S -transferase (GST) M1 and T1 genetic polymorphisms in the development of he patocellular carcinoma (HCC). A total of 84 incident cases of HCC and 375 m atched controls selected from a cohort of 7,342 men (4,841 chronic hepatiti s B carriers and 2,501 noncarriers) who were recruited between 1988 and 199 2 in Taiwan were studied. Neither GST M1/T1 polymorphisms nor plasma levels of various carotenoids were independently associated with HCC, but they mo dulated smoking and/or drinking-related HCC risk. Cumulative exposure to to bacco smoke significantly increased HCC risk in a dose-dependent manner amo ng subjects with low plasma beta-carotene levels (p for trend = 0.047) but not among those with high levels. A statistically significant effect of hab itual alcohol drinking on HCC risk was observed only for those with low pla sma levels of beta-carotene, alpha-carotene, or lycopene and for GST M1 nul l subjects. There was evidence suggesting an interaction between the GST M1 /T1 genotype and certain carotenoids in HCC associated with smoking and dri nking. The strongest effect of smoking and drinking was noted among GST M1 null subjects with low plasma levels of beta-carotene (smoking: adjusted od ds ratio (OR)= 3.54, 95% confidence interval (CI) 1.06-11.83; drinking: OR = 8.28, 95% CI 2.40-28.61).