胸苷酸合成酶基因多态性及烟酒茶嗜好与贲门癌易感性的关系

Thymidylate synthase genotypes, dietary habits and susceptibility of gastric cardia cancer

目的 :研究胸苷酸合成酶TS3′ UTR多态性及其和烟酒茶嗜好相互作用与贲门癌易感性的关系。方法 :在上消化道癌高发区淮安市进行了一个病例对照研究 (贲门癌 89例 ,人群对照 2 2 3例 ) ,调查研究对象的生活习惯 ,采用PCR RFLP技术检测研究对象的TS 3′ UTR基因型。结果 :贲门癌组TS +6/+6bp、+6/-6bp和 -6/-6bp基因型频率分别为7 9%、43 8%和 48 3 % ,与对照组( 8 1%、5 4 3 %和 3 7 7% )相比差异无统计学意义。与携带TS +6bp等位基因且不吸烟、每周饮酒 <2次和饮茶者相比 ,在吸烟、每周饮酒≥ 2次和不饮茶者中 ,携带TS -6/-6bp基因型者发生贲门癌的危险性显著上升 ,调整后的OR分别为 3 99( 95 %CI:1 5 1～ 10 5 0 )、3 2 2 ( 95 %CI :1 2 1～8 5 5 )和 6 14 ( 95 %CI:2 3 9～ 15 77)。结论 :TS 3′ UTR基因多态性影响吸烟。

OBJECTIVE: To evalute interactions between dietary habits and polymorphisms in the 3′-untranslated region (3′-UTR) of thymidylate synthase gene (TS) in the development of gastric cardia cancer. METHODS:We conducted a case-control study with 89 cases of gastric cardia cancer and 223 population-based controls in Huaian City of Jiangsu Province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. TS genotypes were detected by PCR-RFLP method. RESULTS: No significant differences were found between the cases and the controls according to their frequencies of TS 3′-UTR genotypes. Individuals having TS -6 bp/-6 bp genotype and smoking habit were at a significant higher risk for gastric cardia cancer (adjusted OR=3.99,95% CI:1.51-10.50) compared with those having +6bp alleles and no smoking habit. Individuals having TS -6 bp/-6 bp genotype and habit of frequent alcohol drinking were at an increased risk of developing gastric cardia cancer (adjusted OR=3.22,95% CI: 1.21-8.55) compared with those with +6 bp alleles and low consumption of alcohol.Compared with individuals having +6bp alleles and habit of tea drinking, those with TS -6bp/-6bp genotype but without habit of tea drinking had a significant higher risk for gastric cardia cancer(adjusted OR=6.14,95% CI: 2.39-15.77). CONCLUSIONS:Based on environmental factors, different genotypes in TS 3′-UTR may have different susceptibility to gastric cardia cancer.