Genetic polymorphisms of DNA double-strand break repair pathway genes and glioma susceptibility

Abstract

BackgroundGenetic variations in DNA double-strand break repair genes can influence the ability of a cell to repair damaged DNA and alter an individual’s susceptibility to cancer. We studied whether polymorphisms in DNA double-strand break repair genes are associated with an increased risk of glioma development.MethodsWe genotyped 10 potentially functional single nucleotide polymorphisms (SNPs) in 7 DNA double-strand break repair pathway genes (XRCC3, BRCA2, RAG1, XRCC5, LIG4, XRCC4 and ATM) in a case–control study including 384 glioma patients and 384 cancer-free controls in a Chinese Han population. Genotypes were determined using the OpenArray platform.ResultsIn the single-locus analysis there was a significant association between gliomas and the LIG4 rs1805388 (Ex2 +54C>T, Thr9Ile) TT genotype (adjusted OR, 3.27; 95% CI, 1.87-5.71), as well as the TC genotype (adjusted OR, 1.62; 95% CI, 1.20-2.18). We also found that the homozygous variant genotype (GG) of XRCC4 rs1805377 (IVS7-1A>G, splice-site) was associated with a significantly increased risk of gliomas (OR, 1.77; 95% CI, 1.12-2.80). Interestingly, we detected a significant additive and multiplicative interaction effect between the LIG4 rs1805388 and XRCC4 rs1805377 polymorphisms with an increasing risk of gliomas. When we stratified our analysis by smoking status, LIG4 rs1805388 was associated with an increased glioma risk among smokers.ConclusionsThese results indicate for the first time that LIG4 rs1805388 and XRCC4 rs1805377, alone or in combination, are associated with a risk of gliomas.

Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity

“…It is a DNA repair gene in nonhomologous end joining DNA repair pathway [24]. Genetic polymorphisms of XRCC5 were correlated with multiple cancers, including breast cancer, glioma, and hepatocellular carcinoma [25][26][27]. Up to date, there was no association studies reported between XRCC5 polymorphisms and lung cancer.…”

Association of polymorphisms of the xeroderma pigmentosum complementation group F gene with increased glioma risk

“…Currently, identification of novel genetic variants for assessing the early risk of glioma is attracting great interest across the global research community (Silva et al, 2013;Zhao et al, 2013;Hu et al, 2013). Based on genetic information, we may soon be able to determine the genetic etiology of glioma, identify high-risk individuals, and perform targeted therapy according to the genetic characteristics of an individual.…”

Effect of ATM–111 (G>A) Polymorphism on Cancer Risk: A Meta-Analysis

“…Among them, ATM-111 (G>A), a common functional SNP in the promoter region of the ATM gene, was reported to be a binding site of transcription factors that affect the ATM expression Zhang et al, 2010). Early epidemiological studies have identified ATM-111 (G>A) polymorphism as a strong risk factor in lung, breast, and oral cancers (Bau et al, 2010;Lo et al, 2010;Hsia et al, 2013;Zhao et al, 2013;Liu et al, 2014). However, inconsistent results were reported in thyroid cancer, leukemia, and other cancers (Pharoah et al, 2007;Zhao et al, 2013;Damiola et al, 2014;Song et al, 2015).…”