Nucleotide excision repair (NER) is an essential mechanism of the body to defend against exogenous carcinogen-induced DNA damage. Defects in NER may impair DNA repair capacity and, therefore, increase genome instability and cancer susceptibility. To explore genetic predispositions to Wilms tumor, we conducted a case-control study totaling 145 neuroblastoma cases and 531 healthy controls. We systematically selected 19 potentially functional SNPs in six key genes within the NER pathway (ERCC1, XPA, XPC, XPD, XPF, and XPG). The odds ratio (OR) and 95% confidence interval (CI) were calculated to measure the strength of associations. We identified significant associations between two XPD SNPs and Wilms tumor risk. The XPD rs3810366 polymorphism significantly enhanced Wilms tumor risk (dominant model: adjusted OR = 2.12, 95% CI = 1.26–3.57). Likewise, XPD rs238406 conferred a significantly increased risk for the disease (dominant model: adjusted OR = 2.30, 95% CI = 1.40–3.80; recessive model: adjusted OR = 1.64, 95% CI = 1.11–2.44). Moreover, online expression quantitative trait locus (eQTL) analysis demonstrated that these two polymorphisms significantly affected XPD gene expression in transformed fibroblast cells. Our study provides evidence of the association between the two XPD polymorphisms and Wilms tumor risk. However, these findings warrant validation in larger studies.

核苷酸切除修复（NER）是机体抵御外源性致癌物诱导的DNA损伤的重要机制。NER缺陷可能会损害DNA修复能力，因此会增加基因组不稳定性和癌症易感性。为了探讨威尔姆斯肿瘤的遗传易感性，我们进行了一项病例对照研究，总共145例神经母细胞瘤病例和531例健康对照。我们在NER途径的六个关键基因（ERCC1，XPA，XPC，XPD，XPF和XPG）中系统地选择了19个具有潜在功能的SNPs 。计算比值比（OR）和95％置信区间（CI），以测量关联强度。我们发现了两者之间的重要关联XPD SNP和Wilms肿瘤风险。所述XPD rs3810366多态性显著增强肾母细胞瘤的风险（显性模型：调整OR = 2.12，95％CI = 1.26-3.57）。同样，XPD rs238406显着增加了该疾病的风险（主要模型：调整后的OR = 2.30，95％CI = 1.40–3.80；隐性模型：调整后的OR = 1.64，95％CI = 1.11–2.44）。此外，在线表达定量性状基因座（eQTL）分析表明，这两个多态性显着影响转化成纤维细胞中XPD基因的表达。我们的研究提供了两种XPD多态性与Wilms肿瘤风险之间关联的证据。但是，这些发现需要在较大的研究中进行验证。