单核苷酸多态性与原发性肝癌易感性及临床病理学的相关分析
Correlation Analysis of Single Nucleotide Polymorphism with Susceptibility and Clinicopathology of Primary Hepatic Carcinoma

目的：探讨单核苷酸多态性(SNP)与本地区原发性肝癌(PHC)遗传易感性的关系，并探究SNP位点数目与肝癌患者临床病理学的相关性。方法：采用聚合酶链反应–限制性片段长度多态性技术检测234例肝癌患者和234例阴性对照的27个PHC相关SNP位点基因型和等位基因分布频率，并分析SNP位点与PHC遗传易感性、肝癌患者临床病理学和SNP位点数目的相关性。结果：1) miR-34b/c基因rs4938723位点CC基因型(调整OR = 1.736，95%CI：1.036~2.910，P = 0.036)、EGF基因rs4444903位点GG基因型(调整OR = 1.841，95%CI：1.103~3.071，P = 0.019)具有更高的PHC患病风险；KIF1B基因rs17401966位点GG基因型具有更低的PHC患病风险(调整OR = 0.540，95%CI：0.314~0.930，P = 0.026)；分层分析结果显示在男性(P = 0.039)和饮酒(P = 0.025)的人群中EGF基因rs4444903位点基因型GG相比AA + AG基因型PHC发病风险增加；在女性(P = 0.013)、年龄 < 60岁(P = 0.026)及不饮酒(P = 0.039)人群中KIF1B基因rs17401966位点GG基因型相比AA + AG基因型PHC发病风险降低。2) SNP位点数目与门静脉癌栓发生率增加有关(调整OR = 1.122，95%CI：1.005~1.251，P = 0.040)。结论：miR-34b/c基因rs4938723、EGF基因rs4444903、KIF1B基因rs17401966单核苷酸多态性与本地区PHC风险相关，SNP位点数目与肝癌患者临床病理学具有相关性。
Objective: To investigate the relationship between single nucleotide polymorphism (SNP) and ge-netic susceptibility to primary hepatic carcinoma (PHC) in local population, and to explore the cor-relation between the number of SNPs and clinicopathology in patients with PHC. Methods: Poly-merase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype and allele distribution frequency of 27 PHC-associated SNPs in 234 hepatocellular car-cinoma patients and 234 negative controls, and to analyze the correlation between SNPs and genet-ic susceptibility to PHC, clinicopathology of hepatocellular carcinoma patients and the number of SNPs. 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 KIF1B 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), KIF1B rs17401966 GG genotype had a lower risk than AA + AG genotype in female (P = 0.013), age < 60 years (P = 0.026) and non-alcoholic popula-tion (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). Conclusion: Single nucleotide polymor-phisms in miR-34b/c gene rs4938723, EGF gene rs4444903, and KIF1B gene rs17401966 were asso-ciated with PHC risk in the region, and the number of SNPs correlated with clinicopathology in pa-tients with hepatocellular carcinoma.