The phase I metabolizing
enzyme and phase II metabolizing
enzyme play vital roles in
carcinogenesis, but little is known about the changes of their activities in patients with
hepatocellular carcinoma (HCC) secondary to
chronic hepatitis B virus (HBV)
infection. In this study
phenacetin, a probe
drug (1 g for men and 0.85 g for women orally), was applied for the detection of
sulfotransferase 1A1 (SULT1A1) and
cytochrome P4501A2 (
CYP1A2) activities in 82 healthy participants and 148 HCC, 106
cirrhosis, and 41
chronic hepatitis B patients. In addition, a prospective cohort study for susceptibility to HCC was performed in 205 patients with
cirrhosis secondary to chronic HBV
infection. Compared with the healthy participants, SLUT1A1 activity increased by 9.7-fold in the HCC patients (P < 0.01).
CYP1A2 activity did not significantly differ between the healthy participants and HCC patients.
CYP1A2 activity decreased by 91.2% (P < 0.01) and 67.7% (P < 0.05) in the patients with
cirrhosis and
chronic hepatitis B, respectively; SULT1A1 activity did not increase significantly. During an approximate 2-year follow up, three of the 46
cirrhosis patients with elevated SULT1A1 activity and normal
CYP1A2 activity developed HCC, but none of the 159
cirrhosis patients used as parallel controls did (P = 0.012). These results indicate that SLUT1A1 activity is dramatically upregulated in patients with HCC secondary to chronic HBV
infection. The upregulation of SULT1A1 activity is not caused by the
tumor itself. The interaction between SULT1A1 and
CYP1A2 can play an important role in hepatocarcinogenesis in the Chinese population.