Xin Hua Hospital, Shanghai Institute for Pediatric Research, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P.R. China.
Mol Med Rep. 2013 Sep;8(3):919-27. doi: 10.3892/mmr.2013.1589. Epub 2013 Jul 16.
Numerous case-control studies on the association between polymorphisms of key genes involved in methionine remethylation [methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS)] and the susceptibility of cervical intraepithelial neoplasia (CIN) and cervical cancer have provided inconclusive results. The aim of the present meta-analysis was to determine the effects of two MTHFR (C677T and A1298C) and one MS gene polymorphism (A2756G) on the risk of CIN II/III or cervical cancer. Relevant data were retrieved following a systematic search in PubMed, Web of Science, MEDLINE and Wanfang Data up to November 2012. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated from eligible studies by meta-analysis with subgroup analyses stratified by ethnicity. A total of 13 studies with 1,936 cases and 2,858 controls were included in the present meta‑analysis. An increased risk of cervical cancer was found in Asian women with the MTHFR 677T allele (TT vs. CC: OR=1.41, 95% CI=1.07‑1.86, P=0.01; TT vs. CC+CT: OR=1.38, 95% CI=1.08-1.75, P=0.008), while a decreased risk was observed in Caucasian women (TT vs. CC: OR=0.65, 95% CI=0.45-0.93, P=0.02; TT+CT vs. CC: OR=0.7, 95% CI=0.58-0.86, P=0.0005). No effects of MTHFR C677T polymorphism on CIN II/III risk and MTHFR A1298C or MS A2756G polymorphisms on cervical cancer risk were detected. The sensitivity analysis suggested stability of this meta-analysis and no publication bias was detected. The MTHFR 677T allele may enhance the risk of cervical cancer in the Asian female population and play a protective role in Caucasian females. However, limited association is suggested between MTHFR A1298C and MS A2756G polymorphisms with cervical tumorigenesis.
大量关于参与蛋氨酸再甲基化[亚甲基四氢叶酸还原酶（MTHFR）和蛋氨酸合成酶（MS）]关键基因多态性与宫颈上皮内瘤变（CIN）和宫颈癌易感性之间关联的病例对照研究提供的结果尚无定论。本荟萃分析的目的在于确定两个 MTHFR（C677T 和 A1298C）和一个 MS 基因多态性（A2756G）对 CIN II/III 或宫颈癌风险的影响。我们通过系统检索 PubMed、Web of Science、MEDLINE 和万方数据库，检索截至 2012 年 11 月的相关数据。采用荟萃分析合并合格研究的比值比（ORs）及其 95%置信区间（CIs），并根据种族进行亚组分析。本荟萃分析共纳入 13 项研究，包括 1936 例病例和 2858 例对照。结果发现，亚洲女性中 MTHFR 677T 等位基因（TT 与 CC：OR=1.41，95%CI=1.07-1.86，P=0.01；TT 与 CC+CT：OR=1.38，95%CI=1.08-1.75，P=0.008）与宫颈癌风险增加相关，而在高加索女性中则发现风险降低（TT 与 CC：OR=0.65，95%CI=0.45-0.93，P=0.02；TT+CT 与 CC：OR=0.7，95%CI=0.58-0.86，P=0.0005）。MTHFR C677T 多态性与 CIN II/III 风险之间没有关联，MTHFR A1298C 或 MS A2756G 多态性与宫颈癌风险之间也没有关联。敏感性分析表明，该荟萃分析结果稳定，未发现发表偏倚。MTHFR 677T 等位基因可能增加亚洲女性宫颈癌的风险，在高加索女性中发挥保护作用。然而，MTHFR A1298C 和 MS A2756G 多态性与宫颈肿瘤发生之间的相关性有限。
