Genetic polymorphisms of steroid hormone metabolizing enzymes and risk of liver cancer in hepatitis C-infected patients
Rossi, L.; Leveri, M.; Gritti, C.; De Silvestri, A.; Zavaglia, C.; Sonzogni, L.; Silvestri, L.; Civardi, E.; Mondelli, M.U.; Silini, E.M.
Journal of Hepatology 39(4): 564-570
Background/Aims: Genetic polymorphisms of enzymes involved in hormone metabolism can influence hormonal activities and risk of hormone-dependent cancers. As progression of chronic hepatitis C and risk of liver cancer is higher in males than in females, we evaluated whether the polymorphisms of three enzymes participating in the pathway of estrogen and androgen biosynthesis and inactivation, 5alpha-reductase type II (SRD5A2), cytochrome P450c17alpha (CYP17) and catechol-O-methyltransferase (COMT), might affect the expression of hepatitis C virus (HCV)-related liver disease. Methods: The study included 78 healthy subjects and 387 HCV patients: 100 asymptomatic carriers, 105 hepatitis, 90 cirrhosis and 92 hepatocellular carcinomas (HCC). Variant positions SRD5A2 V89L and A49T, CYP17 (-34)T/C and COMT V108M were analysed by polymerase chain reaction and restriction fragment length polymorphism. A cross-sectional study of association was performed, considering carriers as reference category. Results: The CYP17 (-34)C/C genotype was over-represented in HCC patients as compared to carriers (22.5 vs. 11.2%, odds ratio (OR): 2.29, P:0.05). Females mostly contributed to this association (OR: 4.95, P:0.01) and OR values increased in post-menopausal women (OR:6.00, P:0.03). No differences were observed for SRD5A2 and COMT gene polymorphisms. Conclusions: CYP17 high-activity alleles associated with increased circulating levels of estrogens and androgens may affect liver cancer risk in HCV-infected women.