Individuals having variant genotypes of cytochrome P450 2C19 are at increased risk of developing primary liver cancer in Han populations, without infection with the hepatitis virus

Abstract

Recently, many researchers have reported that the genetic polymorphisms of CYP2C19 may account for the interpatient variability of the clinical course in cancers including primary liver cancer (PLC). Besides the genetic polymorphisms of CYP2C19, hepatitis viruses (HV, including HAV, HBV, HCV, HDV, HEV, especially HBV and/or HCV) also account for the interpatient variability of the clinical course in PLC. This research covered the above two factors and divided the patients with PLC into two groups (one group with HBV infection and another without any HV infection) to find out whether the genetic polymorphisms of CYP2C19 have different effects in the progressing of PLC in different groups of patients. Eight hundred sixty-four cancer-free Han people (controls, named group 1), 207 Han PLC patients with HBV infection (group 2), and 55 Han PLC patients without any HV infection (group 3) were involved in this study. A wild-type allele (CYP2C19*1) and two mutated alleles (CYP2C19*2 and CYP2C19*3) were identified. The frequencies of the mutant alleles and genotypes were then compared with each other. The frequencies of the homozygous and heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) in group 3 (25.5 %) were significantly higher than those in other groups (11.9 % in group 1 and 13.5 % in group 2, P = 0.014, 95 % confidence interval (CI)). The differences were statistically significant between group 1 and group 3 (P = 0.004, 95 % CI), but they were not statistically significant between group 1 and group 2 (P = 0.527, 95 % CI). Thus, we conclude that people which were not infected with HV but with the homozygous or heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) of CYP2C19 may have higher possibilities of getting PLC than people with other allelic genotypes (*1/*1, *1/*2, *1/*3) (odds ratio (OR) = 2.523, 95 % CI = 1.329 ~ 4.788). However, in patients with HBV infection, the genetic polymorphisms of CYP2C19 did not seem to be an important factor in the risk of developing PLC (OR = 1.156, 95 % CI = 0.738 ~ 1.810).