Polymorphisms in nucleotide excision repair genes and risk of primary prostate cancer in Chinese Han populations.

Mengyun Wang,Jiucun Wang,Qingyi Wei,Jing He,Yao Zhu,Yajun Yang,Qiaoxin Li,Dingwei Ye,Li Jin,Chengyuan Gu

doi:10.18632/oncotarget.13848

Abstract

Genetic variants of nucleotide excision repair (NER) genes have been extensively investigated for their roles in the development of prostate cancer (PCa); however, the published results have been inconsistent. In a hospital-based case-control study of 1,004 PCa cases and 1,055 cancer-free controls, we genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of NER genes (i.e., XPC, rs2228001 T>G and rs1870134 G>C; XPD, rs13181 T>G and rs238406 G>T; XPG, rs1047768 T>C, rs751402 C>T, and rs17655 G>C; and XPF, rs2276464 G>C) and assessed their associations with risk of PCa by using logistic regression analysis. Among these eight SNPs investigated, only XPC rs1870134 CG/CC variant genotypes were associated with a decreased risk of prostate cancer under a dominant genetic model (adjusted odds ratio [OR] = 0.77, 95% confidence interval [CI] = 0.64–1.91, P = 0.003). Phenotype-genotype analysis also suggested that the XPC rs1870134 CG/CC variant genotypes were associated with significantly decreased expression levels of XPC mRNA in a mix population of different ethnicities. These findings suggested that XPC SNPs may contribute to risk of PCa in Eastern Chinese men.

Highlights

Nucleotide excision repair (NER) is one of the most versatile, well-established DNA repair mechanisms in maintaining genomic stability and integrity [1]
The multivariate logistic regression analyses with a dominant genetic model indicated that XPC rs1870134 CG/ CC was associated with an decreased risk of prostate cancer (PCa), in subgroups of age > 65 [adjusted odds ratio (OR) = 0.78 (0.63-0.97), P = 0.023], body mass index (BMI) ≤ 24kg/m2 [adjusted OR = 0.70 (0.56-0.86), P = 0.0007], ever smokers [adjusted OR = 0.75 (0.60-0.94), P = 0.012], and Gleason score ≤ 7(3+4) [adjusted OR = 0.72 (0.56-0.93), P = 0.012], compared with the homozygous wild-type genotype
Given the possibility that genetic variation in nucleotide excision repair (NER) genes may contribute to variation in the NER capacity, the present study investigated the associations between www.impactjournals.com/oncotarget eight potentially functional single nucleotide polymorphisms (SNPs) of the NER genes and PCa risk

Summary

Introduction

Nucleotide excision repair (NER) is one of the most versatile, well-established DNA repair mechanisms in maintaining genomic stability and integrity [1]. At least eight core genes (i.e., ERCC1, XPA, XPB/ ERCC3, XPC, XPD/ERCC2, XPE, XPF/ERCC4, and XPG/ERCC5) derived from the xeroderma pigmentosm www.impactjournals.com/oncotarget (XP) complementation group, together with other two genes (i.e., CSA /ERCC8 and CSB/ERCC6) encoding proteins linked to Cockayne’s syndrome, are involved in the pathway [2, 3], among which the XP genes were extensively investigated in the development of cancer, both in vivo and in vitro These indicate that reduced DNA repair capacity phenotype may result in genomic instability and carcinogenesis by affecting repair proficiency and that genes involved in the NER pathway are likely to be involved in cancer susceptibility [1, 4,5,6,7,8]. Given that the NER mechanism is important in removal of oxidative DNA damage or DNA adducts in the genome [24], it is biologically plausible to speculate that germline variation in the NER genes may affect the capacity of their encoded DNA repair enzymes to effectively remove DNA adducts or lesions, subsequently leading to PCa risk

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Conclusion