Abstract: Objective To investigate the effect of single nucleotide polymorphism (SNP) in microRNA (miRNA) binding site of BRCA1 gene on the overall survival (OS) of patients with hepatocellular carcinoma (HCC) after operation. Methods A total of 363 HCC patients with undergone radical surgery resection in the Guangxi Medical University Cancer Hospital from June 2004 to December 2013 were included. The Cox proportional hazard model and the Kaplan-Meier method were used to analysis the association between polymorphisms in miRNA binding site of BRCA1 gene and OS of patients with HCC after operation. Results The SNP rs8176318(C>A) in the miRNA binding site of BRCA1 gene was significantly associated with the OS of HCC patients after operation. In the recessive model, after adjusting for hepatitis B virus (HBV) infection, BCLC stage, tumor diameter, tumor thrombus and other factors, the Cox regression analysis showed that HCC patients carrying rs8176318 AA genotypes had a significantly decreased risk of death when compared with those carrying CC/CA genotype (HR=0.675, 95%CI = 0.494-0.922, P=0.014). The Kaplan-Meier curve showed that the median OS of HCC patients with AA genotype was significantly longer than that with CC/CA genotype (46.1 months vs 33.8 months, P=0.049). Using the GTEX database for quantitative trait locus analysis, the rs8176318 A allele was associated with lower BRCA1 mRNA expression levels in liver tissues (P<0.001). Conclusions BRCA1 rs8176318 polymorphism is associated with a lower survival outcomes in patients with HCC after operation, and the A allele is associated with a lower risk of death after operation, but the result needs to be verified by a multi-center study with a larger sample size.

Key words: Hepatocellular carcinoma, BRCA1, microRNA, Single nucleotide polymorphism, Overall survival