Genetic variations in NER pathway gene polymorphisms and Wilms tumor risk: A six-center case–control study in East China

Abstract

The nucleotide excision repair (NER) system is one of the main ways to protect organisms from DNA damage caused by endogenous and exogenous carcinogens. NER deficiency increases genome mutations, chromosomal aberrations, and cancer viability. However, the genetic association between Wilms tumor and NER pathway gene polymorphisms needs to be further validated. We assessed the associations between 19 NER gene polymorphisms and Wilms tumor susceptibility in 416 cases and 936 controls from East China via the TaqMan method. We found that xeroderma pigmentosum group D (XPD) rs238406 and rs13181 significantly decreased the risk of Wilms tumor [adjusted odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.46–0.75, p <.0001; adjusted OR = 0.63, 95% CI = 0.44–0.89, p = .009, respectively]. Furthermore, the rs751402 and rs2296147 polymorphisms in the xeroderma pigmentosum group G (XPG) gene were significantly correlated with an increased risk for Wilms tumor (adjusted OR = 1.47, 95% CI = 1.03–2.09, p = .034; adjusted OR = 2.14, 95% CI = 1.29–3.56, p = .003, respectively). Expression quantitative trait loci (eQTL) analysis revealed that these four polymorphisms may affect the expression of genes that are adjacent to XPD and XPG. Our study provides evidence that XPD and XPG gene polymorphisms are associated with Wilms tumor risk. Nonetheless, these findings should be confirmed in a larger sample size.