The association of six polymorphisms of five genes involved in three steps of nucleotide excision repair pathways with hepatocellular cancer risk
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Bengang Wang1,2,*, Qian Xu1,*, Huai-wei Yang1, Li-ping Sun1, Yuan Yuan1
1Tumor 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
2Hepatobiliary Surgery Department of General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
*These authors contributed equally to this work
Yuan Yuan, e-mail: [email protected]
Keywords: nucleotide excision repair, single nucleotide polymorphism, hepatocellular cancer, interaction
Received: September 07, 2015 Accepted: February 15, 2016 Published: March 07, 2016
Background: 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.
Results: 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.
Methods: 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.
Conclusions: XPC promoter rs1870134 SNP and SNP-SNP interaction were associated with HCC risk.
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