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

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.

Highlights • ERCC1 rs2298881, rs11615 and XPF rs2276466 were associated with increased neuroblastoma risk. • ERCC1 rs2298881 CC and AC/CC genotypes carriers were associated with increased ERCC1 mRNA expression. • This is the most comprehensive study for ERCC1/XPF genes polymorphisms and neuroblastoma risk. In the current study with a Chinese population of 393 neuroblastoma cases and 812 controls, we found that ERCC1 rs2298881, rs11615 and XPF rs2276466 were associated with increased neuroblastoma risk. We also confirmed that ERCC1 rs2298881 CC and AC/CC genotypes carriers were associated with increased ERCC1 mRNA expression. This is by far the most comprehensive study investigating the association between the ERCC1/XPF genes polymorphisms and neuroblastoma risk.