Department of Biomathematics, University of Thessaly School of Medicine, Papakyriazi 22, Larissa 41222, Greece.
Pharmacogenomics. 2009 Aug;10(8):1285-94. doi: 10.2217/pgs.09.59.
Pharmacogenetic studies investigating the relationship between MTHFR gene polymorphisms and response to fluorouracil-based chemotherapy in patients with colorectal cancer have produced inconclusive results. In an attempt to interpret these results, a meta-analysis of all eligible studies published up until January 2009 was carried out.
MATERIALS & METHODS: A total of ten studies relating MTHFR C677T and six studies relating MTHFR A1298C to the response to chemotherapy in patients with colorectal cancer were included in the meta-analysis and random effects pooled odds ratios were estimated. The heterogeneity between studies, the sources of potential bias and the consistency of genetic effects across ethnicities were explored. Cumulative and recursive cumulative meta-analyses were also performed.
For both the C677T and A1298C polymorphisms, the main analysis revealed nonsignificant heterogeneity and a lack of association under the allele contrast, the recessive and dominant models. The subgroup analysis by ethnicity did not change this pattern of results. The lack of stability of the relative change of odds ratio in the recursive cumulative meta-analysis for both polymorphisms indicated the need for more evidence to support a definite lack of association. There was no differential magnitude of the effect in large versus small studies.
The available evidence indicates that MTHFR C677T and A1298C gene polymorphisms cannot be considered as reliable predictors of response to fluorouracil-based chemotherapy in patients with colorectal cancer.
对 MTHFR 基因多态性与结直肠癌患者对氟尿嘧啶为基础的化疗反应之间的关系进行的药物遗传学研究得出的结果并不一致。为了尝试解释这些结果，对截至 2009 年 1 月发表的所有合格研究进行了荟萃分析。
共有 10 项关于 MTHFR C677T 与 6 项关于 MTHFR A1298C 与结直肠癌患者化疗反应的研究被纳入荟萃分析，并估计了随机效应合并优势比。研究间的异质性、潜在偏倚的来源以及遗传效应在不同种族之间的一致性进行了探讨。还进行了累积和递归累积荟萃分析。
对于 C677T 和 A1298C 两种多态性，主要分析显示在等位基因对比、隐性和显性模型下，均无显著的异质性和相关性。按种族进行的亚组分析并未改变这一结果模式。两种多态性的递归累积荟萃分析中，优势比的相对变化的稳定性缺失表明需要更多的证据来支持明确缺乏相关性。在大型研究和小型研究中，效应的大小没有差异。
现有证据表明，MTHFR C677T 和 A1298C 基因多态性不能被视为结直肠癌患者对氟尿嘧啶为基础的化疗反应的可靠预测因子。
