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亚甲基四氢叶酸还原酶(MTHFR)基因多态性与膀胱癌易感性:一项纳入种族、吸烟状况和肿瘤分期的荟萃分析

MTHFR gene polymorphisms and bladder cancer susceptibility: a meta-analysis including race, smoking status and tumour stage.

作者信息

Kouidhi Soumaya, Rouissi Kamel, Khedhiri Sami, Ouerhani Slah, Cherif Mohamed, Benammar-Elgaaied Amel

机构信息

Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences, University of Manar I, Tunis, Tunisia.

出版信息

Asian Pac J Cancer Prev. 2011;12(9):2227-32.

PMID:22296361
Abstract

Epidemiological studies have investigated that functional polymorphisms in the methylene-tetrahydrofolate reductase (MTHFR) gene may play an essential role in bladder carcinogenesis, but the numerous published studies have reported inconclusive results. The objective of the current study was to conduct an updated analysis in order to investigate the association between polymorphisms in the MTHFR gene and risk of bladder cancer. We searched the Pubmed database for all articles published up to March 31, 2011 that addressed bladder cancer and polymorphisms and variants or mutations of MTHFR for analysis using statistical software. Results for two polymorphisms (C677T and A1298C) in 27 case-control were studies from 15 articles indicated individuals carrying the 677T allele (TC or TT+TC) to have a reduction to a 29% or 21% compared to the wild genotype (CC) in mixed populations (OR: 0.71, 95%CI: 0.55-0.93 or OR: 0.79, 95%CI: 0.64-0.97, respectively) and it is shown that there is significant positive associations between A1298C polymorphism and bladder cancer in Africans (OR: 1.24, 95%CI: 1.02-1.52 for C vs.A; OR: 1.35, 95%CI: 1.10-1.66 for CA vs. AA; OR: 1.29, 95%CI: 1.08-1.55 for CC+CA vs. AA). However, no significant relationship was found in two polymorphisms in the stratified analysis by smoking status. Interestingly, individuals carrying the 677T allele (TT+TC) demonstrated a higher percentage of invasive than superficial cases (OR: 1.38, 95%CI: 1.13-1.69). The results from the current update analysis suggest that C677T and A1298C polymorphisms in the MTHFR gene are associated with bladder cancer risk and prognosis. Further evaluation based on more studies with larger groups of patients are now required.

摘要

流行病学研究调查发现,亚甲基四氢叶酸还原酶(MTHFR)基因的功能多态性可能在膀胱癌发生过程中起重要作用,但众多已发表的研究报告结果尚无定论。本研究的目的是进行一项更新分析,以探讨MTHFR基因多态性与膀胱癌风险之间的关联。我们在Pubmed数据库中搜索了截至2011年3月31日发表的所有涉及膀胱癌以及MTHFR多态性、变体或突变的文章,使用统计软件进行分析。来自15篇文章的27项病例对照研究中关于两种多态性(C677T和A1298C)的结果表明,在混合人群中,携带677T等位基因(TC或TT + TC)的个体与野生基因型(CC)相比,风险降低了29%或21%(OR:0.71,95%CI:0.55 - 0.93或OR:0.79,95%CI:0.64 - 0.97),并且显示在非洲人中,A1298C多态性与膀胱癌之间存在显著正相关(C vs. A时OR:1.24,95%CI:1.02 - 1.52;CA vs. AA时OR:1.35,95%CI:1.10 - 1.66;CC + CA vs. AA时OR:1.29,95%CI:1.08 - 1.55)。然而,在按吸烟状况进行的分层分析中,未发现这两种多态性之间存在显著关系。有趣的是,携带677T等位基因(TT + TC)的个体侵袭性病例的比例高于浅表性病例(OR:1.38,95%CI:1.13 - 1.69)。本次更新分析的结果表明,MTHFR基因中的C677T和A1298C多态性与膀胱癌风险及预后相关。现在需要基于更多更大患者群体的研究进行进一步评估。

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