Functional Polymorphisms at ERCC1/XPF Genes Confer Neuroblastoma Risk in Chinese Children

Abstract

Variations in nucleotide excision repair pathway genes may predispose to initiation of cancers. However, polymorphisms of ERCC1/XPF genes and neuroblastoma risk have not been investigated before. To evaluate the relevance of polymorphisms of ERCC1/XPF genes in influencing neuroblastoma susceptibility, we genotyped four polymorphisms in ERCC1/XPF genes using a Chinese population of 393 cases and 812 controls. The results showed that ERCC1 rs2298881 and rs11615 predisposed to enhanced neuroblastoma risk [CA vs. AA: adjusted odds ratio (OR)=1.94, 95% confidence interval (CI)=1.30-2.89, P=0.0012; CC vs. AA: adjusted OR=2.18, 95% CI=1.45-3.26, P=0.0002 for rs2298881, and AG vs. GG: adjusted OR=1.31, 95% CI=1.02-1.69, P=0.038 for rs11615]. Moreover, XPF rs2276466 was also associated with increased neuroblastoma risk (GG vs. CC: adjusted OR=1.66, 95% CI=1.02-2.71, P=0.043). In the combined analysis of ERCC1, we found that carriers with 2-3 risk genotypes were more likely to get risk of neuroblastoma, when compared to those with 0-1 risk genotype (adjusted OR=1.75; 95% CI=1.25-2.45, P=0.0012). Our study indicates that common genetic variations in ERCC1/XPF genes predispose to neuroblastoma risk, which needs to be further validated by ongoing efforts.

Keywords: ERCC1; Neuroblastoma; Polymorphism; Susceptibility; XPF.

Fig. 1

Functional implication of ERCC1 gene rs2298881 and rs11615 polymorphisms. Effect of ERCC1 gene rs2298881 on mRNA expression in (a) 269 HapMap cell lines of all population and (b) 45 HapMap cell lines of unrelated CHB. The genotype of (c) rs2298881 and (d) rs11615 and expression of ERCC1 gene in transformed fibroblasts tissues were searched based on the public database GTEx Portal.