亚甲基四氢叶酸还原酶基因1298A→C多态与食管癌易感性关系的病例对照研究

目的 研究亚甲基四氢叶酸还原酶(MTHFR)基因1298A→C多态及其和生活习惯相互作用与食管癌易感性的关系。方法 在食管癌高发区的淮安市楚州区开展了一项病例对照研究(食管癌患者141例,人群对照228名),调查研究对象的生活习惯,采用聚合酶链反应-限制性片段长度多态性技术检测研究对象的MTHFR 1298A→C基因型。结果 ①食管癌组中MTHFR 1298 AA、AC和CC基因型携带者的比例分别为63.8％、34.0％和2.1％,与对照组的71.9％、28.1％和0.0％相比,差异有统计学意义(X_(MH)~2=6.69,P=0.035)。②在MTHFR 1298C等位基因携带者中,伴有吸烟习惯者发生食管癌的调整OR为3.48(95％CI:1.57～7.71),伴有经常饮酒的习惯者发生食管癌的调整OR为2.91(95％CI:1.20～7.08),无饮茶习惯者发生食管癌的调整OR为3.52(95％CI:1.64～7.54)。MTHFR 1298AC和CC基因型与吸烟、饮酒和不饮茶在食管癌发生中的相互作用系数r分别为3.05、3.69和6.30。结论 MTHFR 1298AC和CC基因型对吸烟、饮酒和不饮茶增加食管癌发生风险的作用有明显的放大效应。

A case-control study on the polymorphisms of methylenetetrahydrofolate reductase 1298A→C and susceptibility of esophageal cancer

OBJECTIVE: To investigate the relationship between polymorphisms of methylenetetra-hydrofolate reductase gene 1298A-->C (MTHFR 1298A-->C) and its susceptibility of esophageal cancer (EC). METHODS: We conducted a case-control study with 141 cases of EC and 228 population-based controls in Huaian city of Jiangsu province, China. Epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were identified by polymerase chain reaction. RESULTS: (1) The frequency of MTHFR 1298AA, AC and CC genotype were 63.8%, 34.0% and 2.1% in EC and 71.9%, 28.1% and 0.0% in controls, respectively (chi(2)(MH) = 6.69, P = 0.035). The frequency of the MTHFR 1298C allele was 0.19 for EC and 0.14 for controls. (2) Individuals having MTHFR 1298C allele and smoking habit were at a significantly higher risk of developing EC (adjusted OR = 3.48, 95% CI: 1.57 - 7.71) compared with those who having AA genotype but no smoking habit. Individuals having MTHFR 1298C allele and habit of frequent alcohol drinking were at an increased risk of developing EC (adjusted OR = 2.91, 95% CI: 1.20 - 7.08) compared with those with AA genotype and low consumption of alcohol. Individuals having MTHFR 1298C allele but no habit of tea drinking had a 3.52-fold (95% CI: 1.64 - 7.54) increased risk of developing EC compared with tea drinkers with AA genotype. As compared with subjects having AA genotype, low consumption of alcohol, no smoking habit but having habit of drinking tea, the individuals having 1298C allele, habits of frequent alcohol drinking, smoking but no habit of tea drinking had a 12.64-folds (95% CI: 1.39 - 114.65) increased risk of developing EC. CONCLUSION: Results in the present study suggested that there was a coordinated effect between MTHFR 1298 genotypes and habits of smoking, alcohol drinking and tea consumption in the development of EC.