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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。
Objective: To investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) and the risk of colorectal cancer (CRC). METHODS: A hospital-based case-control study of colorectal cancer (300 new cases of colorectal cancer and 300 controls) was performed. The polymorphisms of MTHFRC677T and A1298C related to folic acid metabolism were detected and correlated with the risk of colorectal cancer. RESULTS: No effects of MTH-FR677 and 1298 polymorphisms on CRC alone were observed, but the risk of colorectal cancer was found to be increased in the MTHFR-677CT / 1298AC combination with an OR of 2.32 (95% CI, 1.10-4.92, P = 0.027). There was no statistically significant correlation found between the risk of MTHFR haplotypes and cronosomal genes and CRC. There was an interaction between MTHFRC677T and A1298C genes and smoking prevalence (likelihood ratio test, P = 0.002, P = 0.001). The risk of colorectal cancer was increased by 2.09 for MTHFR-677T alleles in smokers <16 years (95% CI, 1.07-4.04). However, the risk of MTHFR-1298AA genotype was significantly lower in colorectal cancer patients with smoking ≥ 16 years, OR = 0.37 (95% CI, 0.17-0.80). There was an interaction between MTHFRC677T polymorphism and alcohol consumption (likelihood ratio test, P = 0.000). Conclusion: MTHFR-677CT / 1298AC combined gene is a risk factor for CRC. MTHFR has some interactions with smoking and drinking.