Polymorphisms in DNA Repair Genes and Susceptibility to Glioma in a Chinese Population

Wei-Ran Pan,Gang Li,Jun-Hong Guan

doi:10.3390/ijms14023314

Abstract

The excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), and X-ray repair cross-complementing group 1 (XRCC1) genes appear to protect mammalian cells from the harmful effects of ionizing radiation. We conducted a large case-control study to investigate the association of polymorphisms in ERCC1 C118T, ERCC1 C8092A, XRCC1 A194T, XRCC1 A194T, and XRCC3 C241T, with glioma risk in a Chinese population. Five single nucleotide polymorphisms (SNPs) were genotyped, using the MassARRAY IPLEX platform, in 443 glioma cases and 443 controls. Association analyses based on an χ2 test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each SNP. For XRCC1 Arg194Trp, the variant genotype T/T was strongly associated with a lower risk of glioma cancer when compared with the wild type C/C (OR = 2.45, 95% CI = 1.43–4.45). Individuals carrying the XRCC1 399A allele had an increased risk of glioma (OR = 1.33, 95% CI = 1.02–1.64). The XRCC3 241T/T genotype was associated with a strong increased glioma risk (OR = 3.78, 95% CI = 1.86–9.06). Further analysis of the interactions of two susceptibility-associated SNPs, XRCC1 Arg194Trp and XRCC3 Thr241Met, showed that the combination of the XRCC1 194T and XRCC3 241T alleles brought a large increase in glioma risk (OR = 2.75, 95% CI = 1.54–4.04). XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 C241T, appear to be associated with susceptibility to glioma in a Chinese population.

Highlights

Tumors of the central nervous system (CNS) account for about 2% of all cancers, and its morbidity is about 4.2/105 to 5.4/105 people per year, worldwide [1]
X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, the variant genotype T/T was strongly significantly associated with a lower risk of glioma cancer, when compared with the wild-type C/C, with an adjusted odds ratio (OR) of
Our findings strongly indicate that polymorphisms in XRCC1 Arg194Trp and X-ray repair cross-complementing groups 3 (XRCC3) Thr241Met contribute to glioma susceptibility, and are in line with those of previous studies showing that the XRCC1 194T allele is associated with increased glioma risk [19,20]

Summary

Introduction

Tumors of the central nervous system (CNS) account for about 2% of all cancers, and its morbidity is about 4.2/105 to 5.4/105 people per year, worldwide [1]. The only established environmental risk factors are ionizing radiation and ultraviolet rays, and the low exposure to these types of radiation, in daily life, may explain the low incidence rate of this cancer [3,4]. Both types of radiation cause an accumulation of DNA damage, including oxidative. X-ray repair cross-complementing groups 3 (XRCC3) participates in DNA double-strand break/recombination repair, and likely participates in HRR [10]. We conducted a large case-control study to investigate whether there is an association between glioma risk and polymorphisms in these three genes, in a Chinese population

Results

Discussion

Study Subjects

Genotyping

Statistical Analysis

Conclusions