XRCC1 and XRCC3 variants and risk of glioma and meningioma

Abstract

Several single nucleotide polymorphisms (SNPs) affecting DNA repair capacity and modifying cancer susceptibility have been described. We evaluated the association of SNPs Arg194Trp, Arg280His, and Arg399Gln in the X-ray cross-complementing group 1 (XRCC1) and Thr241Met in the X-ray cross-complementing group 3 (XRCC3) DNA repair genes with the risk of brain tumors. The Caucasian study population consisted of 701 glioma (including 320 glioblastoma) cases, 524 meningioma cases, and 1,560 controls in a prospective population-based case-control study conducted in Denmark, Finland, Sweden, and the UK. The studied SNPs were not significantly associated with the risk of brain tumors. The highest odds ratios (ORs) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma (OR = 1.32; 95% confidence interval, CI, 0.97-1.81), glioblastoma (OR = 1.48; 95% CI, 0.98-2.24), and meningioma (OR = 1.34; 95% CI, 0.96-1.86). However, in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors: Among others, carriers of both homozygous variant genotypes, i.e., XRCC1 Gln399Gln and XRCC3 Met241Met, were associated with a three-fold increased risk of glioma (OR = 3.18; 95% CI, 1.26-8.04) and meningioma (OR = 2.99; 95% CI, 1.16-7.72). In conclusion, no significant association with brain tumors was found for any of the polymorphisms, when examined one by one. Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors.

Association between the XRCC1 Arg194Trp Polymorphism and Glioma Risk: an Updated Meta-analysis

“…Among them, the XRCC1 Arg194Trp variant located in the proliferating cell nuclear antigen (PCNA) binding region, which suggests that this mutation may be result in gliomagenesis. However, these studies have failed to yield a consistent conclusion (Kiuru et al, 2008;Liu et al, 2009;McKean-Cowdin et al, 2009;Rajaraman et al, 2010;Custodio et al, 2011;Hu et al, 2011;Zhou et al, 2011;Liu et al, 2012;Luo et al, 2013;Pan et al, 2013;Wang et al, 2012;Xu et al, 2013).…”

“…One study conducted in region of Europe with 700 glioma patients and 1556 controls reported that no association between the Arg194Trp polymorphism and glioma cancer risk (Kiuru et al, 2008). The other studies in USA consisted of a total sample size (1514 cases and 2755 controls) showed that Arg194Trp did not confer an effect on glioma (Liu et al, 2009;McKean-Cowdin et al, 2009;Rajaraman et al, 2010).…”

“…Third, glioma is known as a multifactor disease, due to lack of detailed data, such as environmental factors, physical inactivity and dietary state factors, thus the gene-gene and gene-environment interactions were not addressed in this meta-analysis. Fourth, several articles indicated that demographic parameters are not well adjusted statistically (Kiuru et al, 2008;McKean-Cowdin et al, 2009). Fifth, misclassifications of genotypes may also impact the results because cases were not verification by other gold standard methods in several studies, and the quality control of genotyping was also not well-verification in some articles.…”

Molecular Epidemiology of Primary Brain Tumors

“…We have listed about 20 epidemiological studies reporting positive associations between DNA repair polymorphisms and cancer risk (Table 1 [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] ). Only a small proportion of studies were large (five studies were more than 500 pair cases and controls) and population based; however, some consistencies in results are apparent.…”

DNA Repair Gene ERCC1 and XPD Polymorphisms Predict Glioma Susceptibility and Prognosis

“…Currently, the etiology of glioma has not been completely understood. Previous studies have reported that a number of single nucleotide polymorphisms (SNPs) in DNA repair gene may modify glioma risk (Wang et al, 2004;Wrensch et al, 2005;Kiuru et al, 2008;Liu et al, 2009;Zhou et al, 2009;Rajaraman et al, 2010;Hu et al, 2011;Yosunkaya et al, 2010;Zhou et al, 2011). However, the clinical value of most glioma-associated molecular aberrations in terms of their significance as diagnostic, prognostic or predictive molecular markers has remained unclear (Batchelor et al, 2004;Ohgaki et al, 2004;Houillier et al, 2006).…”