亚甲基四氢叶酸还原酶基因多态性、饮酒与结直肠癌关系的病例对照研究

目的 研究亚甲基四氢叶酸还原酶(MTHFR)基因多态与结直肠癌(包括结肠癌、直肠癌)易感性的关系。方法 应用聚合酶链反应(PCR)和限制性片段长度多态性方法(RFLP),检测了126例结直肠癌患者和343名正常对照的MTHFR C677T和A1298C两个位点基因多态,并比较不同基因型单独、联合时与结直肠癌风险的关系,以及两个多态位点与饮酒的联合作用。结果MTHFR677T和1298C突变基因在对照组中的频率分别为39.7％和17.1％。1298C突变基因携带者与野生型相比,患结直肠癌的风险均降低;在携带677C和1298C等位基因组合个体中,结直肠癌的风险略有降低(OR=0.718,95％CI:0.367～1.407),同时含677T和1298A等位基因者,结直肠癌的风险降低1倍;同时含有677T和1298C等位基因者,结直肠癌的风险降低4倍,直肠癌的风险降低7倍(OR=0.304,95％CI:0.108～0.852)。在过去饮酒者中,1298A等位基因携带者结直肠癌风险性增加2倍(OR=3.307,95％CI:0.521～17.698)。结论 MTHFR C667T和A1298C位点多态性在结直肠癌发生过程中起着一定作用,携带MTHFR 1298AC基因多态型者过去饮酒是结直肠癌的危险因素。

A case-control study on the polymorphisms of methylenetetrahydrofolate reductases.drinking interaction and susceptibility in colorectal cancer

Objective To investigate the relationship between methylenetetrahydrofolate reductases(MTHFR) polymorphisms and colorectal cancer susceptibility. Methods A case-control study of 126patients and 343 healthy controls was conducted to investigate the roles of MTHFR C677T and A1298Cpolymorphisms in colorectal cancer development. Genotypes of C677T and A1298C polymorphisms wereanalyzed by polymerase chain resction-restriction fragment length polymorphism (PCR-RFLP) methods.Results The frequencies of MTHFR 677T and 1298C allele were 39. 7% and 17. 1%, respectively. Afteradjustment for age and sex, the MTHFR 1298C alleles seemed to have reduced association on the risk ofcolorectal cancer comparing to wild types. Among those with 677T and 1298A alleles, a decreased risk ofcolorectal cancer was observed: a 4-fold decrease in colorectal cancer risk (OR=0.552,95% CI: 0. 265-1.150) in those with 677T and 1298C alleles. Men who were ex-drinkers and with MTHFR 1298C allelehad a 2-fold increase in risk of colorectal cancer (OR=3.307, 95% CI: 0. 521-17.698) while no increasedrisk was seen among those current-drinkers. Conclusions This study suggested that certain MTHFRC677T and A1298C might be associated with the risk of colorectal cancer development. The interactionbetween MTHFR 1298AC polymorphisms and ex-drinking might also serve as a risk factor of colorectalcancer.