亚甲基四氢叶酸还原酶基因多态性与结直肠癌易感性的关系

Correlation of genetic polymorphisms of methylenetetrahydrofolate reductase with susceptibility of colorectal cancer

目的:研究亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因C677T、A1298C多态性与结直肠癌易感性的关系.方法:在江苏省进行了一个病例-对照研究(结直肠癌患者315例,人群对照371例),调查研究对象的生活习惯,抽取静脉血,提取白细胞DNA,采用PCR-RFLP检测研究对象的MTHFR C677T、A1298C基因型.结果:1)男女合计的结直肠癌组、结肠癌组和直肠癌组与对照组之间的MTHFR C677T、A1298C基因型分布频度和等位基因频度差异无统计学意义,MTHFR C677T、A1298C基因多态与结直肠癌、结肠癌和直肠癌的易感性无显著相关.2)在男性中,结肠癌组MTHFR C677T T/T基因型的频度为24.6%,明显高于对照组的14.8%,但差异无统计学意义,X2=3.42,P=0.064.与C677T C等位基因携带者相比,T/T基因型者发生结肠癌的危险性显著升高,其性别、年龄、居住地区及吸烟、饮酒和饮茶习惯调整后的OR为2.15(95%CI:1.07～4.33).与同时携带MTHFR C677T C等位基因和A1298C A/A基因型者相比,男性的MTHFR C677T T/T和A1298C A/A基因型携带者发生结肠癌的危险性显著升高,其调整OR为2.64(95%CI:1.20～5.81),而他们发生直肠癌的危险性则明显降低,(调整OR=0.47,95%CI:0.22～1.03).结论:MTHFR C677T基因多态可以影响男性结、直肠癌的易感性,MTHFR A1298C多态与C677T多态在对男性结、直肠癌易感性的影响中有协同作用.

OBJECTIVE：To study the relation ship between genetic polymorphisms of methylenetetrahydrofolate reductase （MTHFR） C677T or A1298C and the susceptibility of colorectal cancer. METHODS： A case-control study was conducted with 315 cases of colorectal cancer and 371 population-based controls in Jiangsu Province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR C677T and A1298C genotypes were detected by PCR RFLP. RESULTS： 1）When men and women were assessed together, the frequencies of the MTHFR C677T and A1298 genotypes or their alleles were not significantly different between the controls and colon cancer or rectal cancer cases. No significant relation was observed between MTHFR C677T or A1298C polymorphisms and colon or rectal cancer susceptibility. 2）Among males, individuals who had MTHFR C677T T/T genotype were at a significantly higher risk of developing colon cancer （sex-, age-, residence-, smoking, alcohol drinking-, tea consumption-adjusted OR= 2. 15, 95% CI： 1.07-4.33） compared with those who had C677T C allele. Individuals who had C677T T/T and A1298C A/A genotypes were at an increased risk of developing colon cancer （adjusted OR=2.64,95% CI： 1.20- 5.81） compared with those with C677T C allele and A1298C A/A genotypes among males. On the contrary, individuals who had C677T T/T and A1298C A/A genotypes were at an decreased risk of developing rectal cancer （adjusted OR= 0.47, 95% CI： 0. 22-1.03）. CONCLUSION： Polymorphisms of the MTHFR C677T can influence susceptibility to colon or rectal cancer, and there is a synergic effect between MTHFR A1298C A A and C677T T/T genotypes among males.