Association between the xeroderma pigmentosum complementation group F (XPF)rs2276466 located in the excision repair cross complementation group 4 (ERCC4) gene and cancer susceptibility has been widely investigated. However, results thus far have remained controversial. A meta-analysis was performed to identify the impact of this polymorphism on cancer susceptibility. PubMed, Embase and Science-Web databases were searched systematically up to May 20, 2018, to obtain all the records evaluating the association between the rs2276466 polymorphism and the risk of all types of cancers. We used the odds ratio (OR) as a measure of effect, and pooled the data in a Mantel-Haenszel weighed random-effects meta-analysis to provide a summary estimate of the impact of this polymorphism on gastrointestinal cancer, neurogenic cancer and other cancers (breast cancer and SCCHN). All the analyses were carried out in STATA 14.1.11 case–control studies that consisted of 5730 cases and 6756 controls, were eventually included in our meta-analysis. The significant association was observed between the XPFrs2276466 polymorphism and neurogenic cancer susceptibility (recessive model: OR = 1.648, 95% CI = 1.294–2.098, P<0.001). Furthermore, no significant impact of this polymorphism was detected on decreased gastrointestinal cancer risk (dominant model: OR = 1.064, 95%CI = 0.961–1.177, P = 0.233). The rs2276466 polymorphism might play different roles in carcinogenesis of various cancer types. Current evidence did not suggest that this polymorphism was directly associated with gastrointestinal susceptibility. However, this polymorphism might contribute to increased neurogenic cancer risk. More preclinical and epidemiological studies are still imperative for further evaluation

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ABSTRACT. We aimed to investigate the role of 4 single nucleotide polymorphisms of the xeroderma pigmentosum complementation group F (XPF) gene (rs3136038, rs1799798, rs1800067, and rs2276466) in glioma, and the roles of gene-gene interactions in the risk of developing this type of cancer. We collected samples from 225 glioma cases and 262 controls and genotyped the rs3136038, rs1799798, rs1800067, and rs2276466 polymorphisms using a 384-well plate format with the Sequenom MassARRAY platform. Individuals carrying the rs1800067 GG genotype were more likely to have an increased risk of glioma when compared with carriers of the A/A genotype in a co-dominant model, with an odds ratio (OR) [95% confidence interval (CI)] of 2.85 (1.14-7.76). However, we did not find an association with increased risk of glioma for the polymorphisms rs3136038, rs1799798, and rs2276466 XPF polymorphisms and glioma risk in XPF. The combination genotype of the rs1800067 G allele and the rs2276466 G allele was associated with a moderate risk of glioma (OR = 1.71, 95%CI = 1.02-2.87). Our study suggests that the rs1800067 genetic variant of XPF functions in the development of glioma.