The single nucleotide polymorphism arg399gln rs25487 in XRCC1 gene is a breast cancer risk factor, but is not related to tp53 mutation status

Abstract

Genetic changes in DNA repair genes, such as X-ray cross-complementing group1 (XRCC1), can cause modifications in the capacity of damaged DNA repair and affect the risk of cancer. Several mutations in TP53, which is a tumor suppressor gene, have been associated with breast cancer. In this study, it is aimed to evaluate the association of genetic variation in XRCC1rs25487 single nucleotide polymorphism (SNP) with TP53 mutation and breast cancer risk. In this research, 200 breast cancer women and 200 controls from the Iranian-Azeri population, Iran, were enrolled. Genomic DNA was extracted from the whole blood of controls patients. PCR-RFLP was carried out to genotype all participants for XRCC1rs25487SNP. Determination of possible mutations of TP53 in exons 5,6,7, and 8 were performed on 30 cancerous breast tissues through sequencing the amplified fragments. Our results of the case-control study indicated that the GA genotype of XRCC1 gene in rs25487polymorphism has a significantly risk effect on the breast cancer in the dominant genetic model (OR: 1.580, 95% CI: (1.025-2.436); p-value =0.049) and also GA genotype of XRCC1 gene in rs25487polymorphism has a protective effect on breast cancer in overdominant genetic model (OR: 0.591, 95% CI (0.395-0.886), p-value = 0.014). Furthermore, genotypes of this SNP did not associate with the clinical specifications of the patients and P53 mutation status. Sequencing results showed the mutational spectrum of P53 in the studied cases. According to the results of this study, in some of the genetic models, XRCC1SNP appears to be a modulator of breast cancer risk in Iranian East-Azerbaijan women. However, there was no correlation between XRCC1SNP and TP53 mutation status of the tumor.