亚甲基四氢叶酸还原酶基因多态性与结肠癌发生关系的荟萃分析

Relevance of Genetic Polymorphism of Methylene Tetrahydrofolate Reductase and Susceptibility to Colonic Cancer: a Meta-analysis

背景:亚甲基四氢叶酸还原酶(methylenetetrahydrofolatereductase,MTHFR)基因多态性与结肠癌发生密切相关,目前多数病例对照研究结果表明MTHFRTT型多态性对结肠癌发生具有保护作用,尤其是在叶酸充足和摄入低乙醇的个体。目的:探讨亚甲基四氢叶酸还原酶基因多态性与结肠癌的相关性。方法:通过文献检索收集肿瘤组和非肿瘤组的病例对照研究,剔除不符合要求的文献,在全面文献回顾的基础上进行荟萃分析。结果:共有12篇符合条件的文献纳入分析,荟萃分析结果表明,以野生型677CC的基因型为参照,携带TT基因型个体发生结肠癌的危险性明显下降,OR为0.84(95%CI:0.76～0.94);1298CC型相对AA型发生结肠癌的危险性为0.85(95%CI:0.72～1.01)。携带677TT基因型同时摄入高叶酸的个体相对于CC/CT基因型伴摄入低叶酸者发生结肠癌的危险性明显下降,OR为0.76(95%CI:0.52～1.10);摄入高叶酸的1298AA和AC/CC携带者相对于携带AA基因型伴摄入低叶酸者发生结肠癌的危险性显著降低,OR分别为0.78(95%CI:0.63～0.95)和0.78(95%CI:0.64～0.96)。携带677TT基因型者不论乙醇摄入高低,发生结肠癌的危险性均为0.92,而CC/CT基因型同时摄入高乙醇者发生结肠癌的危险性为1.34(95%CI:0.92～1.95);1298位点基因多态性与结肠癌危险性似乎同乙醇摄入无多大关联。结论:MTHFR多态性与结肠癌发生危险性有关,677TT型和高叶酸摄入明显降低肿瘤发生危险性,而高乙醇摄入在677CC/CT基因型个体中有增加结肠癌发生的趋势。

Background： A close relationship between methylene tetrahydrofolate reductase （MTHFR） polymorphism and colonic cancer has recently been found. Most case-control studies showed that MTHFR 677TT genotype had a protective effect on colonic cancer, especially with adequate folate intake and low alcohol consumption. Aims： To study the relevance of MTHFR polymorphism and susceptibility to colonic cancer. Methods： Through literatures review on the same topic and similar methods used, the OR values in these studies were incorporated by meta-analysis to assess the relevance of MTHFR polymorphism and susceptibility to colonic cancer. Results： Twelve papers were selected. Meta-analysis found that the MTHFR 677TT genotype showed a significantly reduced risk of colonic cancer compared with the wild type 677CC genotype （OR=0.84, 95% CI： 0.76-0.94）,and 1298CC allele-carrier showed an inverse relationship on the risk of colonic cancer compared to the wild type 1298AA genotype （OR=0.85, 95% CI： 0.72-1.01）. Adequate intake of folate was a protective factor for colonic cancer and MTHFR 677TT polymorphism showed a significant additive protective effect （OR=0.76, 95% CI： 0.52-1.10）. This was also found in MTHFR 1298AA and AC/CC genotype （OR=0.78, 95% CI： 0.63- 0.95; OR=0.78, 95% CI： 0.64-0.96, respectively）. The 677CC/CT genotype was associated with a significant increase in the risk when alcohol consumption was high （OR=1.34, 95% CI： 0.92-1.95）, but it was not found in 677Tr genotype （OR= 0,92）. And no association was found between MTHFR A 1298C polymorphism and the risk of colonic cancer when alcohol consumption was considered. Conclusions： The results suggest that MTHFR C677T polymorphisms are associated with risk of colonic cancer, whereas MTHFR 677TT genotype and adequate folate intake show an inverse relationship. Excessive alcohol consumption is associated with increased risk of colonic cancer in 677CC/CT genotype.