Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
PLoS One. 2012;7(7):e38606. doi: 10.1371/journal.pone.0038606. Epub 2012 Jul 2.
Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive.
METHODOLOGY/PRINCIPAL FINDINGS: In this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI), we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154), and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR=0.87, 95% CI=0.76-1.00, P=0.049, P=0.723 for heterogeneity test, I(2) =0). Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student's t test for a recessive model: P=0.046). No publication bias was found by using the funnel plot and Egger's test.
This meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies.
着色性干皮病互补组 F（XPF 或 ERCC4）在保护遗传不稳定性和致癌作用方面发挥着关键作用。一系列流行病学研究已经检验了 XPF 多态性与癌症风险之间的关联，但结果仍不确定。
方法/主要发现：在这项对 47639 例癌症病例和 51915 例对照的荟萃分析中，通过搜索三个电子数据库（即 MEDLINE、EMBASE 和 CNKI），我们总结了 29 篇文献中的 43 项病例对照研究，这些研究涉及 XPF 的四个常见多态性（即 rs1800067、rs1799801、rs2020955 和 rs744154），我们没有发现任何与总体癌症风险相关的统计学证据。然而，在分层分析中，我们发现 XPF-rs1799801 与白种人群癌症风险降低有关（4845 例病例和 5556 例对照；隐性模型：OR=0.87，95%CI=0.76-1.00，P=0.049，P=0.723 用于异质性检验，I²=0）。进一步的基因型-表型相关性分析表明，纯合变异 CC 基因型携带者的 XPF 表达水平高于 TT 基因型携带者（隐性模型的学生 t 检验：P=0.046）。漏斗图和 Egger 检验未发现发表偏倚。
本荟萃分析表明，XPF 四个 SNP 与癌症总体风险之间缺乏统计学证据。然而，XPF-rs1799801 可能与白种人群的癌症风险相关，需要在大型、精心设计的前瞻性研究中进一步验证。
