Glioma risk associates with polymorphisms of DNA repair genes, XRCC1 and PARP1

Abstract

Cancer develops through interactions between polygenic and environmental factors, and changes in DNA repair pathway can increase susceptibility to tumours. XRCC1 and PARP1 are two proteins that act cooperatively in base excision repair (BER) of DNA. The polymorphisms of genes coding these proteins may effect their action in BER pathway. In this study, we aimed to investigate the associations between glioma risk and XRCC1 Arg399Gln and PARP1 Val762Ala polymorphisms per se and in combination. XRCC1 Arg399Gln and PARP1 Val726Ala polymorphisms were investigated by PCR-RFLP method in 119 glioma patients and 180 cancer-free control subjects. The results were statistically analysed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ2 tests. Glioma patients in this study had significantly higher frequencies of XRCC1 Arg399Gln polymorphism both in homozygote (GG) and heterozygote (AG) status (31% and 56%, respectively) (p < 0.001), and also increased frequency of 399Gln (G) allele (59%) (p < 0.001). Val/Ala (VA) genotype of PARP1 Val762Ala polymorphism was significantly more in the control group (p = 0.02). The combined genotypes of XRCC1 AG or GG with PARP1 VA or AA, and XRCC1 AG or GG with PARP1 VV were more represented in the glioma patients (p = 0.001 and 0.003, respectively). We conclude that XRCC1 Arg399Gln polymorphism is a significant risk factor, and 399Gln (G) allele carries a 3.5 times greater risk for glioma, while PARP1 Val/Ala genotype may be protective against it. We also suspect that in the presence of a polymorphic (G) allele of XRCC1, the plausible protective effect of PARP1 VA genotype may be greatly suppressed.