DNA错配修复基因MSH2和MLH1单核苷酸多态性与食管癌发生风险相关性研究

Study of esophageal cancer risk associated with polymorphisms of DNA mismatch repair genes MSH2 and MLH1

目的:探讨DNA错配修复基因MSH2和MLH1单核苷酸多态性对于食管癌易感性的潜在作用。方法:采用医院为基础的病例-对照研究方法,应用PCR-RFLP检测包括正常对照132例,食管癌患者169例MSH2c.2063T>G和MLH1IVS14-19A>G两个基因多态性位点的基因型。通过Logistic回归分析计算出比值比(OR)和95%置信区间(95%CI),估计不同基因型频率分布与食管癌发生风险的关系。结果:MSH2c.2063T>G携带突变等位基因个体发生食管癌的风险是非携带者的3.24倍。MLH1IVS14-19A>G突变等位基因携带者发生食管癌风险是非携带者的1.58倍。对MSH2和MLH1基因交互作用分析发现两突变基因型携带者发生食管癌风险大大增加并具有显著的统计学意义。结论:DNA错配修复基因MSH2c.2063G突变等位基因和MLH1IVS14-19G突变等位基因可能在促成食管癌发生过程起到一定作用。

Objective： This article dealt with whether single nucleotide polymorphisms （SNPs） of DNA mismatch repair genes MSH2 and MLH1 potentially contributed to EC susceptibility. Methods： A hospital based case control study with 169 EC cases and 132 controls in a Chinese population was conducted. We genotyped two SNPs MSH2 c. 2063T2〉G and MLHt IVS14-19A〉G using PCR-RFI.P and then carried out statistical analysis by calculating the adjusted odds ratios （OR） and 95% confidence intervals （95% CI）. Results： Carriers of the MSH2 c. 2063 G allele were at a higher risk of developing EC with the TT genotype as reference （OR= 3.24, 95%CI=1.41-9.05, P=0. 009）. Also for MLH1 IVS14- 19A〉G individuals with at least one G allele （A/G or G/G） had a 1.58-fold increased risk for EC development compared to those who bore the A/A Mid-type genotype （OR= 1.58, 95%CI= 1.56 --5.66, P=0. 015）. Moreover, statistically significant variant genotypic interaction was suggested between MSH2 and MLH1 due to a much increased predisposition to EC （P=0. 016）. Conclusions.. Our findings indicated that genetic variants in MSH2 c. 2063 G allele and MLH1 IVS14--19 G allele conferred risk for the process of esophageal tumorigenesis.