microRNA靶序列单核苷酸多态性与胃癌易感性关系

Correlation between single nucleotide polymorphism of microRNA target site and gentic susceptibility of gastric cancer

目的 研究炎性相关基因IL-1F5（interleukin-1 factor 5）的3’非编码区microRNA（miRNA）靶序列单核苷酸多态性（SNP）与胃癌易感性关系。方法 采用1∶1频数匹配病例-对照研究对研究对象进行基因分型，应用多因素条件logistic回归及多因素降维法（MDR）分析SNP与胃癌易感性的关系及其与环境因素的交互作用。结果 rs2472188位点GC基因型（OR=1.50，95%CI=1.13-1.99）和rs2515401位点CT基因型（OR=1.42，95%CI=1.09-1.86）是胃癌的易感基因；单体型分析显示，单体型1（CCGCA）（OR=2.08，95%CI=1.27-3.40）、单体型4（CTATA）（OR=1.98，95%CI=1.48-2.66）、单体型5（CTATC）（OR=10.13，95%CI=4.43-23.16）可增加胃癌发病风险，而单体型2（CTACA）（OR=0.18，95%CI=0.12-0.28）、单体型3（CTACC）（OR=0.37，95%CI=0.23-0.59）、单体型9（GCGTC）（OR=0.39，95%CI=0.27-0.58）可降低胃癌发病风险；具有rs2472188、rs2515401以及rs2515402组合的人群是胃癌发病风险的高危人群（OR=6.17，95%CI=4.61-8.36）。结论 rs2472188位点GC基因型、rs2515401位点CT基因型是胃癌的易感基因型，多位点联合作用对于胃癌的发生可能有协同作用。

Objective To assess the correlation between single nucleotide polymorphism（SNP）of microRNA（miRNA）target site and the gentic susceptibility of gastric cancer. Methods A 1：1 matched case-control study was adopted in this study.Genotyping was carried out among the subjects.Conditional logistic regression model and multifactor-dimensionality reduction（MDR）method were used to analyze the correlation between SNP of interleukin-1 factor 5（IL-1F5）and genetic susceptibility of gastric cancer.The gene-environment interaction was also analyzed. Results GC genotype in rs2472188 locus（odds ratio [OR]=1.50,95% confidence interval [95%CI]=1.13-1.99）and CT genotype in rs2515401 locus（OR=1.42,95%CI=1.09-1.86）were susceptible genotypes for gastric cancer.Haplotype analysis showed that haplotype 1（CCGCA）（OR=2.08,95%CI=1.27-3.40,haplotype 4（CTATA）（OR=1.98,95%CI=1.48-2.66）and haplotype 5（CTATC）（OR=10.13,95%CI=4.43-23.16）increased the risk of occurrence of gastric cancer,whereas haplotype 2（CTACA）（OR=0.18,95%CI=0.12-0.28）,haplotype 3（CTACC）（OR=0.37,95%CI=0.23-0.59）and haplotype 9（GCGTC）（OR=0.39,95%CI=0.27-0.58）decreased the risk. Conclusion Genotypes of GC in rs2472188 locus and CT in rs2515401 locus may be susceptible genotypes for gastric cancer.Combined effects of multigene alleles and multi-locus genotype may have a synergistic effect in the carcinogenesis of gastric cancer.