Wang Bengang, Xu Qian, Yang Huai-Wei, Sun Li-Ping, Yuan Yuan
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.
Hepatobiliary Surgery Department of General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Oncotarget. 2016 Apr 12;7(15):20357-67. doi: 10.18632/oncotarget.7952.
Hundreds of single nucleotide polymorphisms (SNPs) of the genes encoding nucleotide excision repair (NER) proteins are involved in every step of the DNA recognition-unwinding-incision process, which may affect cancer risk. However, only a limited number of studies have examined the association of NER SNPs with hepatocellular cancer (HCC) risk.
In screening stage, single-locus analysis showed that six SNPs in five genes were associated with HCC risk, including three risk SNPs (XPA rs10817938, XPC rs1870134 and ERCC2 rs238417) and three protective SNPs (ERCC1 rs2298881 and rs3212961, and ERCC5 rs873601). In verification stage, only XPC rs1870134 was verified to be associated with HCC risk (P = 4.7 × 10-4). Furthermore, multivariate logistic regression and MDR analysis consistently revealed a gene-gene interaction among ERCC1 rs2298881 and XPC rs1870134 SNPs associated with HCC risk (Pinteraction = 0.023). When analyzing the effect of the positive SNP on the mRNA expression, we found XPC rs1870134 GG genotype which was associated with an increased HCC risk showed lower XPC mRNA expression.
This study designed as "screening-verification" experiments and included a total of 1472 participants (570 HCC patients vs. 902 controls). We explored 39 SNPs in eight genes involved in NER Pathways, including XPA, XPC, DDB2, ERCC3, ERCC2, ERCC1, ERCC4 and ERCC5, using Sequenom MassARRAY and KASPar platform. Eighty-six cases of HCC and the neighboring noncancerous tissues were subjected to the measurement of mRNA expression level of the promising gene.
XPC promoter rs1870134 SNP and SNP-SNP interaction were associated with HCC risk.
编码核苷酸切除修复（NER）蛋白的基因存在数百个单核苷酸多态性（SNP），它们参与DNA识别-解旋-切割过程的每一步，这可能会影响癌症风险。然而，仅有有限数量的研究探讨了NER SNPs与肝细胞癌（HCC）风险的关联。
在筛选阶段，单基因座分析显示五个基因中的六个SNP与HCC风险相关，包括三个风险SNP（XPA rs10817938、XPC rs1870134和ERCC2 rs238417）以及三个保护性SNP（ERCC1 rs2298881和rs3212961，以及ERCC5 rs873601）。在验证阶段，仅XPC rs1870134被证实与HCC风险相关（P = 4.7×10-4）。此外，多因素逻辑回归和MDR分析一致揭示了与HCC风险相关的ERCC1 rs2298881和XPC rs1870134 SNPs之间存在基因-基因相互作用（P相互作用 = 0.023）。在分析阳性SNP对mRNA表达的影响时，我们发现与HCC风险增加相关的XPC rs1870134 GG基因型显示出较低的XPC mRNA表达。
本研究设计为“筛选-验证”实验，共纳入1472名参与者（570例HCC患者与902名对照）。我们使用Sequenom MassARRAY和KASPar平台探索了参与NER途径的八个基因中的39个SNP，包括XPA、XPC、DDB2、ERCC3、ERCC2、ERCC1、ERCC4和ERCC5。对86例HCC病例及其邻近的非癌组织进行了有前景基因的mRNA表达水平测定。
XPC启动子rs1870134 SNP及SNP-SNP相互作用与HCC风险相关。
