MTHFR基因多态和饮酒习惯与结直肠癌易感相关性的研究

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)与结直肠癌(CRC)风险的关系。方法:进行了以医院为基础的结直肠癌病例对照研究(结直肠癌新发病例300例,对照300例)。对叶酸代谢相关基因MTHFRC677T和A1298C多态性进行了检测,并与结直肠癌风险关联进行了分析。结果:未观察到MTH-FR677和1298多态单独对CRC发生的影响,但发现MTHFR-677CT/1298AC组合型发生结直肠癌的风险增加,OR值为2.32(95%CI,1.10～4.92,P=0.027)。未发现MTHFR单倍型和双体型基因与CRC的风险之间存在统计学的显著关联。MTHFRC677T和A1298C基因与吸烟程度之间存在交互作用(似然比检验,P=0.002,P=0.001),在吸烟<16包年者中,MTHFR-677T等位基因患结直肠癌的风险增加2.09(95%CI,1.07～4.04),而在吸烟≥16包年者中,MTHFR-1298AA基因型患结直肠癌的风险明显下降,OR值为0.37(95%CI,0.17～0.80)。MTHFRC677T多态与饮酒之间存在交互作用(似然比检验,P=0.000)。结论:MTHFR-677CT/1298AC组合型基因是CRC的危险因素,MTHFR与吸烟、饮酒之间存在一定的交互作用。

Relationship of genetic polymorphisms in methylenetetrahydrofolate reductase and alcohol drinking with the risk of colorectal cancer

OBJECTIVE:To determine the relationship of polymorphisms in methylenetetrahydrofolate reductase(MTHFR C677TandA1298C)with the risk of colorectal cancer(CRC).METHODS:A hospital-based case-control study consisting of 300 colorectal cancer cases and 300 controls matched on age and sex was conducted.The polymorphisms of MTHFRC677T and A1298C was detected and the association between polymorphisms of MTHFR and CRC was analized.RESULTS:No significant relationship of the C677T and A1298C genotype alone with the risk of cancer was observed.It was found that MTHFR-677CT/1298AC was significantly associated with the risk of CRC(OR=2.32,95%CI,1.10-4.92,P=0.027).No association was found between MTHFR haplotype and duplex gene and risk of CRC.Interactions were found between the extent of smoking and MTHFR C677T and A1298C(likelihood test,P=0.002,P=0.001,respectively).The risk of CRC increased by 2.09(95%CI,1.07-4.04)in smokers less than 16 packs every year with MTHFR-677T allele,as significantly decreased as OR:0.37,95%CI,0.17-0.80 in smokers more than 16 packs every year with MTHFR-1298AA genotype.Interation between drinking and MTHFRC677T was found(likelihood test,P=0.000).CONCLUSIONS:The risk factor of CRC is MTHFR-677CT/1298AC combined genotype.There are interactions between MTHFR polymorphism and smoking or drinking.