Zhu Jinhong, Fu Wen, Jia Wei, Xia Huimin, Liu Guo-Chang, He Jing
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Clinical Laboratory, Molecular Epidemiology Laboratory, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China.
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Mol Ther Nucleic Acids. 2018 Sep 7;12:854-860. doi: 10.1016/j.omtn.2018.08.002. Epub 2018 Aug 8.
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损伤的一种重要机制。NER缺陷可能会损害DNA修复能力，从而增加基因组不稳定性和癌症易感性。为了探究肾母细胞瘤的遗传易感性，我们开展了一项病例对照研究，共纳入145例神经母细胞瘤病例和531例健康对照。我们系统地在NER途径中的六个关键基因（ERCC1、XPA、XPC、XPD、XPF和XPG）中选择了19个具有潜在功能的单核苷酸多态性（SNP）。计算比值比（OR）和95%置信区间（CI）以衡量关联强度。我们发现两个XPD SNP与肾母细胞瘤风险之间存在显著关联。XPD rs3810366多态性显著增加了肾母细胞瘤风险（显性模型：校正OR = 2.12，95% CI = 1.26 - 3.57）。同样，XPD rs238406使该疾病风险显著增加（显性模型：校正OR = 2.30，95% CI = 1.40 - 3.80；隐性模型：校正OR = 1.64，95% CI = 1.11 - 2.44）。此外，在线表达定量性状位点（eQTL）分析表明，这两个多态性显著影响转化成纤维细胞中的XPD基因表达。我们的研究提供了两个XPD多态性与肾母细胞瘤风险之间存在关联的证据。然而，这些发现需要在更大规模的研究中进行验证。
