XRCC1 Arg399Gln Polymorphism Confers Risk of Breast Cancer in American Population: A Meta-Analysis of 10846 Cases and 11723 Controls

Abstract

BackgroundIn the X-ray repair cross-complementing group 1 (XRCC1) gene, a polymorphism, Arg399Gln (rs25487), has been shown to change neoconservative amino acid and thus result in alternation of DNA repair capacity. Numerous studies have investigated the association between Arg399Gln and breast cancer risk in the American population, but yielding inconsistent results. This study aimed to clarify the role of this polymorphism in susceptibility to breast cancer.MethodsLiteratures were searched in multiple databases including PubMed, Springer Link, Ovid, EBSCO and ScienceDirect databases up to April 2013. A comprehensive meta-analysis was conducted to estimate the overall odds ratio (OR), by integrating data from 18 case control studies of 10846 cases and 11723 controls in the American population.ResultsOverall, significant association was observed between the Arg399Gln polymorphism and breast cancer risk under the random-effects model (OR for dominant model = 1.12, 95% CI: 1.02–1.24, P heterogeneity = 0.003; OR for additive model = 1.07, 95% CI: 1.01–1.14, P heterogeneity = 0.017). Further sensitivity analysis supported the robust stability of this current result by showing similar ORs before and after removal of a single study.ConclusionsThis meta-analysis suggests that the XRCC1 Arg399Gln polymorphism may significantly contribute to susceptibility of breast cancer in the American population.

Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women

“…Polymorphisms in XRCC1 have been connected to functional changes at the protein level by influencing the DNA repair rate and may results in carcinogenesis (Vodicka et al, 2007). In this study, we have no statistical evident to associate the variant in XRCC1 rs1799782 and rs25487 SNPs to breast cancer risk in Malaysian women but latest metaanalysis studies showed that variant in both SNPs were significantly increased the risk of breast cancer (Wu et al, 2011;Liu et al, 2013;Bu et al, 2014;Feng et al, 2014). Interestingly, a study conducted by Ye et al revealed that breast cancer patients with Gln/Gln genotype in XRCC1 rs25487 SNP were associated with a longer survival rate after chemotherapy treatment when compared to wildtype genotype (Ye et al, 2012), indicating the prognostic value of this SNP in breast cancer patients receiving chemotherapy.…”

“…Taken together, there is significant evidence showing that these three genes are involve in modulating the pathway in the development of breast cancer. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) were inconclusively associated to breast cancer risk in case-control or meta-analysis studies in different populations (Wu et al, 2006;Bu et al, 2014;Dai et al, 2014;Ding et al, 2014;Feng et al, 2014;Guo et al, 2014;Qin et al, 2015), but association of these SNPs to breast cancer in Southeast Asia populations, especially in Malaysian women was unquestionably insufficient. Therefore, this pilot study investigates the association of these SNPs, together with etiology factors such as age and ethnicity, to breast cancer risk in Malaysian women.…”

XRCC1 Gene Polymorphisms and Breast Cancer Risk: A Systematic Review and Meta-analysis Study

“…As we pooled all the individual studies, we compare our result with previous meta-analysis. The last metal analysis of Arg399Gln and risk of breast cancer was done by Bu et al (2014) that included 18 case control studies and just pooled the studies for American population.Their results were similar to our result except that they were able to detect statistically significant association just for certain genetic model (dominant and additive). Another meta-analysis by Wu K. included 44 case and control studies and their finding was similar to our study (they report association under recessive and dominant model) (Wu et al, 2011).…”

Impact of DNA Repair Genes Polymorphisms on Incidence and Prognosis of Breast Cancer in an Egyptian Cohort

“…Individuals who had the Gln allele were reported to be more prone to breast cancer under different genetic model (dominant, recessive and additive). [11,12,13] Yet controversial results were reported, as many studies reported no association between breast cancer and XRCC1 gene polymorphisms, [14] or even decrease of breast cancer risk. [15] NER pathway removes a huge variety of damage to the human genome.…”