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.
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Acknowledgement
The authors thank the patients and volunteers, who participated in this study. This study was not financially supported by any governmental or non-governmental funds, and the authors report no conflicts of interest.
Author contributions
Each author in this paper contributed to various aspects of this study: Clinical data collected, and blood samples obtained by B. Kucukyuruk, DNA isolation and genotyping performed by C.B.Gurel, patient recruitment by B. Kucukyuruk and M. Uzan, study designed by I. Onaran and G. Kanigur-Sultuybek, data interpretation and writing of the paper performed by E. Yosunkaya.
Declaration of interest: Only the authors are responsible for the content and writing of this manuscript.