Estrogen Receptor Alpha Polymorphisms Associated with Susceptibility to Hepatocellular Carcinoma in Hepatitis B Virus Carriers

摘要

Backqround & Aims: Overexpression of estrogen receptors (ESRs) is implicated in the development of hepatocellular carcinoma (HCC) in both animal models and humans. We examined whether the ESR1 polymorphisms were related to HCC risk among chronic hepatitis B virus (HBV) carriers. Methods: Six ESR1 polymorphisms, which are (TA)n repeat in the promoter, T29C at codon 10 in exon 1, Pvu Ⅱ and Xba Ⅰ site in intron 1, C136474G at codon 325 in exon 4 and A252966G in intron 5, were genotyped in 248 HCC patients and 239 controis. The associations with the susceptibility to HCC were estimated by logistic regression. Allele-specific transcription difference of ESR1 mRNA was performed by real-time quantitative PCR. Results: We observed a statistically significantly increased susceptibility to HCC associated with the homozygous alleles with a high number of TA repeats (assigned as H/H genotype, odds ratio [OR] = 2.66, 95% confidence interval [CI] = 1.44-4.94,P= 0.0018), T29C C/C genotype (OR = 2.31, 95% Cl = 1.25-4.26, P= 0.0076) and Pvu Ⅱ C/C genotype (OR =2.19, 95% Cl = 1.27-3.78, P = 0.0048), compared with the homozygous alleles with a low number of TA repeats (assigned as L/L genotype), T29C T/T and Pvu Ⅱ T/T genotype, respectively. In accordance, the relative mRNA levels of the at-risk C allele of T29C were consistently higher than those of the T allele in heterozygous cells.Conclusions: Our findings suggest that the genetic polyrnorphism in ESR1 may play a role in mediating Susceptibility to HCC in Chinese HBV carriers.