Correlation Analysis Of Single Nucleotide Polymorphisms With Susceptibility And Prognosis Of Primary Hepatic Carcinoma

Objective :Primary hepatic carcinoma(PHC),which ranks fourth in global tumor mortality,greatly affects patients’ quality of life and shortens their survival time.The research on the third-generation genetic marker,namely single nucleotide polymorphism(SNP),has become a hot spot at present.In recent years,some studies have reported that some single nucleotide polymorphisms are associated with the occurrence and development of primary hepatic carcinoma.Different populations of single nucleotide polymorphisms lead to differences in susceptibility,progression and prognosis of liver cancer.Therefore,the aim of this study was to investigate the relationship between single nucleotide polymorphism(SNP)and genetic susceptibility to primary hepatic carcinoma in this region and the correlation between the number of SNPs and clinicopathology of patients with liver cancer.Meanwhile,TP53 gene,as a highly mutated oncogene,is involved in almost all human tumors,and this study investigated the correlation between single nucleotide polymorphism of TP53 gene and the prognosis of primary hepatic carcinoma patients in this region.Methods: Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used to detect the genotype and allele distribution frequency of 27 primary hepatic carcinoma-associated SNPs in 234 hepatocellular carcinoma patients and 234 negative controls,and to analyze the correlation between SNPs and genetic susceptibility to primary hepatic carcinoma,clinicopathology of hepatocellular carcinoma patients and the number of SNPs.Also,213 patients with postoperative primary hepatocellular carcinoma were genotyped for TP53 gene rs1625895,rs9895829,and rs28934578,and the relationship between SNPs and patient prognosis was analyzed.Results:1.The miR-34b/c gene loci rs4938723 CC genotype(adjusted OR=1.736,95% CI:1.036～2.910,P=0.036)and EGF gene loci rs4444903 GG genotype(adjusted OR=1.841,95% CI:1.103～3.071,P=0.019)had a higher risk of PHC.The KIF1 B gene loci rs17401966 GG genotype(adjusted OR=0.540,95% CI:0.314～0.930,P=0.026)had lower risk of PHC.The stratification analysis showed that EGF rs4444903 GG genotype had a higher risk than AA+AG genotype in male(P=0.039)、and alcoholic population(P=0.025),KIF1 B rs17401966 GG genotype had a lower risk than AA+AG genotype in female(P=0.013)、age<60 years(P=0.026)and nonalcoholic population(P=0.039).2.More SNPs resulted in higher incidence of portal vein carcinoma thrombosis(adjusted OR=1.122,95% CI:1.005～1.251,P=0.040).3.Tumor T3+T4 staging(HR=2.145,95%CI: 1.139-4.037,P=0.018),tumor diameter ≥5cm(HR=2.021,95% CI: 1.040-3.928,P=0.038),TP53 gene rs1625895 AA genotype(HR=2.169,95%CI:1.015-4.637,P=0.046),palliative resection(HR=2.245,95%CI: 1.216-4.143,P=0.010),perioperative blood transfusion(HR=1.901,95%CI: 1.050-3.440,P=0.034),tumor multiplicity(HR=2.157,95%CI:1.139-4.085,P=0.018)and having cirrhosis(HR=2.546,95%CI: 1.248-5.193,P=0.010)were risk factors for the postoperative prognosis in patients with hepatocellular carcinoma.Conclusion:1.Single nucleotide polymorphisms in miR-34b/c gene rs4938723,EGF gene rs4444903,and KIF1 B gene rs17401966 were associated with PHC risk in the region.2.The number of SNPs correlated with portal vein carcinoma thrombosis.3.TP53 gene rs1625895 polymorphism is associated with prognosis in patients with primary hepatocellular carcinoma.