中国汉族人群hMLH1基因多态与乳头状甲状腺癌的遗传易感性

目的 探讨中国汉族人群中错配修复hMLH1(human MutL homolog 1)基因多态与乳头状甲状腺癌(papillary thyroid carcinoma,PTC)遗传易感性的关系.方法 采用以医院为基础的1:1配对病例对照研究设计;应用聚合酶链反应、限制性片段长度多态性、等位基因特异性寡核苷酸探针杂交和DNA测序技术检测204对乳头状甲状腺癌患者和健康对照的位于hMLH1基因启动子的-93G＞A、第12外显子的1151T＞A和第8外显子的655A＞G等3个多态性.结果 单因素分析发现,以115TT基因型为参照,1151TA基因型可以使PTC发病风险边缘性升高,1151TA+AA基因型可使PTC发病风险显著性升高,OR值分别为2.15(95%CI:0.99～4.85)和2.15(95%CI:1.02～4.69).2×4叉生分析显示,以-93GG和1151TT基因型为参照,同时拥有-93GA+AA和1151TA+从基因型个体,其PTC的发病风险边缘性升高,OR值为2.50(95%CI:0.96～6.67);以655AA和1151TT基因型为参照,同时拥有655AA和1151TA+AA基因型的个体,其PTC的发病风险显著性升高,OR值为2.15(95%CI:1.02～4.73).遗传和环境多因素条件losistic回归分析结果显示,1151TA+AA基因型,既往CT检查史,肿瘤家族史,负性生活事件,经常吃海鲜是PTC的危险因素,OR值分别为6.79(95%CI:3.18～14.49),3.35(95%CI:1.93～5.80),39.03(95%CI:3.70～41.60)和3.98(95%CI:1.81～8.73);经常吃水果是PTC的保护因素,OR值为0.56(95%CI:0.35～0.90).结论 hMLH1基因1151TA+从基因型、既往CT检查史、肿瘤家族史、负性生活事件、经常吃海鲜是PTC的危险因素,经常吃水果是保护因素.

Study on genetic polymorphism of human mismatch repair gene hMLH1 and susceptibility of papillary thyroid carcinoma in Chinese Han people

Objective To explore the associations between the single nucleotide polymorphism of human mismatch repair gene hMLH1 and the papillary thyroid carcinoma(PTC)in Chinese Han people.Methods A hospital baaed 1:l matched case-control study was carried out.The single nucleotide polymorphism(-93G＞A,1151T＞A and 655A＞G)for 204 pairs of cases with PTC as well as healthy controls was identified by PCR-RFLP,PCR-ASO and DNA sequencing.Results With univariate analysis,we found that compared to 1151TT genotype,the TA genotype could increase the PTC risk marginaly,with odds ratio(OR)of 2.15(95%CI:0.99-4.85);While the mutant genotypc TA+AA could increase the PTC risk statistically significant,with OR of 2.15(95%CI:1.02-4.69).With2×4 cross-over study,we found that compared to-93GG and 1151TT genotypes,individuals with both-93GA+AA and 1151TA+AA could increase the PTC risk marginally,with OR of 2.50(95%CI:0.96-6.67);While,compared to 655AAand 1151TT genotypes,individuals with both 655AA and 1151TA+AA could illCregse the PTC risk statistically significant,with OR of 2.50(95%CI:1.02-4.73).Multivariate and conditional logistic regression analysis showed the genotype of 1151TA,the history of receiving CT diagnosis,the history of tumor,the negative life events and eating seafood frequently could increase the risk of PTC,with OR of 6.79 (95%CI:3.18-14.49),3.35(95% CI:1.93-5.80),39.03(95% CI:3.70-41.60)and 3.98 (95%CI:1.81-8.73); While,eating fruit frequently could decrease the PTC risk.Conclusion The 11S1TA +AA genotype,the history of receiving CT diagnosis,the history of tumor,the negative life events and eating seafood frequently were the risk factors of PTC,while eating fruit frequently was the protective factor.