Yosunkaya Elif, Kucukyuruk Baris, Onaran Ilhan, Gurel Cigdem B, Uzan Mustafa, Kanigur-Sultuybek Gonul
Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Turkey.
Br J Neurosurg. 2010 Oct;24(5):561-5. doi: 10.3109/02688697.2010.489655.
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.
癌症通过多基因和环境因素之间的相互作用发展而来，DNA修复途径的改变会增加患肿瘤的易感性。XRCC1和PARP1是两种在DNA碱基切除修复（BER）中协同作用的蛋白质。编码这些蛋白质的基因多态性可能会影响它们在BER途径中的作用。在本研究中，我们旨在调查胶质瘤风险与XRCC1 Arg399Gln和PARP1 Val762Ala多态性本身及其组合之间的关联。采用PCR-RFLP方法对119例胶质瘤患者和180例无癌对照受试者进行了XRCC1 Arg399Gln和PARP1 Val726Ala多态性检测。使用χ2检验计算优势比（OR）及其95%置信区间（95%CI）对结果进行统计学分析。本研究中的胶质瘤患者在纯合子（GG）和杂合子（AG）状态下，XRCC1 Arg399Gln多态性的频率均显著更高（分别为31%和56%）（p < 0.001），399Gln（G）等位基因的频率也有所增加（59%）（p < 0.001）。PARP1 Val762Ala多态性的Val/Ala（VA）基因型在对照组中显著更多（p = 0.02）。XRCC1 AG或GG与PARP1 VA或AA的组合基因型，以及XRCC1 AG或GG与PARP1 VV的组合基因型在胶质瘤患者中更为常见（分别为p = 0.001和0.003）。我们得出结论，XRCC1 Arg399Gln多态性是一个显著的风险因素，399Gln（G）等位基因患胶质瘤的风险高3.5倍，而PARP1 Val/Ala基因型可能对其具有保护作用。我们还怀疑，在存在XRCC1多态性（G）等位基因的情况下，PARP1 VA基因型可能的保护作用可能会被大大抑制。
