The Effect Of BIM Genetic Polymorphism On HBV-related Hepatocellular Carcinoma Outcomes

Objective:To explore the effect of BIM genetic polymorphism associated with HBV-related hepatocellular carcinoma outcomes.Methods:176 patients with HBV-related hepatocellular carcinoma were recruited,106 patients with TACE treatment as TACE group and 70 patients received supportive and symptomatic treatment as control group.The demographic and clinical data were collected at the establishment of HBV-related HCC diagnosis.The informations of treatment were recorded in each patients and the survival data of the patients were prospectively gathered until December 31,2016 by a combination of outpatient,inpatient and telephone methods.All patients had been received the nucleotide sequence by high-throughput Taqman probe method.Overall survival differences were analyzed by Kaplan-Meier curve and compared by log-rank test.Cox regression was used to perform multiple analyses to identify factors associated with the OS of the patients.Multifactor Dimensionality Reduction(MDR)program was used to test for potential interactions among significant SNPs.Therefore the connection of BIM single nucleotide polymorphisms with HBV-related hepatocellular carcinoma were analyzed.Results: Results showed that rs761706 of BIM C allele-containing genotypes as well as rs724710 genotype CT and allele T were significantly associated with longer OS(P=0.016 and P=0.008,respectively)in all patients;in multivariate analysis,rs761706 C allele-containing genotypes was independently associated with longer OS(hazard ratio(HR),8.913;95% confidence interval(CI),1.150–13.315;P = 0.029).rs761706 C allele-containing genotypes or rs724710 genotype CT and allele T or rs3827537 genotype TA and allele A were significantly associated with longer OS in patients receiving transcatheter arterial chemoembolization(TACE)(P =0.0043 、P=0.003 and P = 0.023,respectively);in multivariate analysis genotype TA and allele A was independently associated with longer OS(HR=18.654;95%CI: 2.082-167.16;P=0.009).In patients receiving supportive and symptomatic treatment,rs761706 C allele-containing genotype was significantly associated with longer OS(P<0.001),but we not found any effect influences the suivival time in multivariate analysis.MDR analysis revealed that the interaction between the three SNPs(rs761706、rs761706 、 rs3827537)modulated the clinical outcomes of HBV-related hepatocellular carcinoma(TBA=0.6147,CVC:10/10,P:0.012-0.013).Conclusion:These findings suggest that rs761706 C/T,rs724710 C/T and rs3827537 T/A of BIM genetic polymorphisms may affect the prognosis of HBV-related hepatocellular carcinoma patients.