PD-1基因多态位点rs2227982和rs10204525与肺癌关联性分析

Association analysis between genetic polymorphism rs2227982 and rs10204525 of PD-1 and lung cancer

目的:PD-1基因是肿瘤免疫调节的关键靶点,本研究探讨PD-1基因的多态性位点(rs2227982和rs10204525)与肺癌发生的关系。方法:应用病例对照研究的方法,收集肺癌患者302例和健康对照320例,采用Taqman Genotyping方法对收集的样本进行基因分型,并分析其与临床特征关系。结果:发现携带rs2227982 C等位基因,增加肺癌发病风险[OR=1.31,95%CI(1.03~1.64)](P=0.019),基因型分析发现在相加性模型(additive model)[OR=1.30,95%CI(1.04~1.62)]和隐性模型(recessive model)[OR=0.62,95%CI(0.42~0.97)]中与肺癌发生具有相关性。进一步通过调整吸烟、年龄和饮酒的影响后,rs2227982基因型仍与肺癌发生显著相关[OR=1.38,95%CI(1.08~1.77)],P<0.001。但rs2227982基因型与肺癌的病理类型和临床分期无关联,研究结果未发现rs10204525基因型与肺癌发生相关。结论:PD-1基因多态性与肺癌发生相关,rs2227982-CC基因型人群的肺癌发病率高于rs2227982-CT和rs2227982-TT基因型,通过多中心及大样本的验证,可作为潜在的遗传易感性分子标记。

Objective:The PD-1 gene is a key target in tumor immune regulation.This study investigated the association between the genetic polymorphisms(rs2227982 and rs10204525)in PD-1 gene and lung cancer.Methods:A case-control study was performed between 302 patients with lung cancer and 320 healthy controls.The collected samples were genotyped by Taqman Genotyping method,and the association with clinical characteristics was analyzed.Results:Our study found that the rs2227982 C allele increased the risk of lung cancer,OR=1.31,95%CI(1.03~1.64)(P=0.019)comparing to rs2227982 T allele,and further analysis found that rs2227982 genotypes significantly associated with lung cancer in the additive model[OR=1.30,95%CI(1.04~1.62)]and recessive model[OR=0.62,95%CI(0.42~0.97)].After adjustment the effects of smoke,age and alcohol,rs2227982 genotypes were still significantly associated with lung cancer[OR=1.38,95%CI(1.08~1.77)].However,the rs2227982 genotype had no association with the pathological types and clinical stages in lung cancer.And the rs10204525 was not related to lung cancer.Conclusion:The results show that the genetic polymorphism of PD-1 associates with lung cancer,and the rs2227982-CC genotype shows genetic susceptibility to lung cancer,comparing to rs2227982-TT and rs2227982-CT.It can be used as a potential genetic marker after validation by multi-center and large sample analysis.