中国人群MTHFR基因多态性与乳腺癌易感性Meta分析

Association between MTHFR polymorphism and breast cancer susceptibility in Chinese population:A Meta-analysis

目的：评估中国人群亚甲基四氢叶酸还原酶（methylene tetra hydro folate reductase，MTHFR）C677T（rs1801133）多态性及其与乳腺癌易感性的相关性。方法：全面检索PubMed、web of Science、EBSCO、中国知网（CNKI）、维普（VIP）、万方和中国生物医学文献数据库（CBM），收集关于中国人群MTHFRC677T（rs1801133）SNP与乳腺癌易感性的相关研究，以比值比（OR）及95％CI可信区间（95％CI）为效应指标，根据异质性大小采用固定或随机效应模型进行合并分析，并进行偏倚评估和敏感性分析。应用RevMan5．2及Statal2．0软件进行统计学处理。结果：共纳入16篇病例一对照研究，包括3625例患者，对照4621例。Meta分析结果显示，总体人群中MTHFRC677T（rs1801133）TT基因型与乳腺癌易感性明显相关，TT与CC比较，OR=1．52，95％CI为1．14～2．01，P=0．004；TT与CC＋CT比较，OR=1．51，95％CI为1．17～1．94，P=0．001，而T等位基因及TT＋TC基因型无显著相关性，P〉0．05。按地区进行亚组分析结果显示，MTHFRC677T（rs1801133）多态性与北方人群乳腺癌易感性有明显相关性，TT＋CT与CC比较，OR=1．55，95％CI为1．15～2．09；T与C比较，0R=1．62，95％CI为1．30～2．03；TT与CC比较，OR=2．79，95％CI为1．78～4．36；TT与CC＋CT比较，0R=2．51，95％CI为1．51～4．16。而MTHFRC677T（rs1801133）多态性与南方人群乳腺癌易感性无显著相关性，TT＋CT与CC比较，0R=0．98，95％CI为0．86～1．11；T与C比较，0R=0．95，95％CI为0．80～1．13；TT与CC比较，0R=1．21，95％CI为0．93～1．57；TT与CC十CT比较，0R=1．23，95％CI为0．97～1．56，P〉0．05。结论：MTHFRC677T（rs1801133）多态性与中国北方人群乳腺癌易感性有关，而可能与南方人群乳腺癌易感性无关，TT基因型及T等位基因可能是北方人群乳腺癌易感的危险因素。

OBJECTIVE： To comprehensively evaluate the association between MTHFR polymorphism and breast cancer susceptibility with meta-analysis. METHODS：General searches of electronic databases Pubmed,Web of Science, EB- SCO,CNKI, VIP,Wanfang and CBM were performed to retrieve published case-control studies investigating the associa- tion between MTHFR polymorphism and susceptibility to breast cancer in Chinese population. The pooled odds ratios （ORs） with 95 % confidence intervals （95 %CIs） were calculated using fixed effect or random-effect methods based on the absence or presence of significant heterogeneity. Publication bias and sensitivity analysis were also assessed. All statistical analyses were conducted with RevManS. 2 and STATA12.0 software. RESULTS： A total of 16 case-control studies invol- ving 3 625 cases and 4 621 controls were included in the meta-analysis. The results showed that the TT genotype was significantly associated with breast cancer susceptibility for overall [TT vs CC： OR = 1.52,95 % CI （ 1. 14,2.01 ）, P = 0. 004;TT vs CC＋CT： OR=1.51,95%CI （1.17,1.94）,P=0. 001],and no association of the TT genotype and T allele carrier with breast cancer susceptibility was observed（P〉0.05）. The subgroup analysis based on region revealed that the MTHFR C677T （rs1801133） polymorphism was significantly correlated with susceptibility to breast cancer in north Chi- na population [TT＋CT vs CC ：OR=1. 55,95%CI （1. 15,2.09）;T vs C ： OR=1. 62,95%CI （1.30,2.03）;TT vs CC： OR=2.79,95%CI（1.78,4.36） ;TT vs CC＋CT： OR =2.51,95%CI （1.51,4. 16）] ,but not in south China population [TT＋CT vs CC：OR=0.98,95%CI（0.86,1.11）;T vs C：OR=0. 95,95%CI（0.80,1. 13）;TT vs CC：OR= 1.21.95%CI （0.93,1. 57）;TT vs CC＋CT： OR= 1. 23,95%CI （0. 97,1. 56）,P〉0. 05]. CONCLUSION： The MTHFR C677T （rs1801133） polymorphism is significantly associated with susceptibility to breast cancer in north China population but not in south China population,and the TT genotype and T allele are potentially risk factors for breast cancer susceptibility in north China population.