Association of Functional Polymorphisms of the XRCC4 Gene with the Risk of Breast Cancer: A Meta-analysis

Abstract

<br/><b>Objective</b>: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for DNA double-strand breaks(DSB) in the non-homologous end-joining (NHEJ) pathway. Several potentially functional polymorphisms of theXRCC4 gene have been implicated in breast cancer risk, but individually published studies showed inconclusiveresults. The aim of this meta-analysis was to investigate the association between XRCC4 polymorphisms and therisk of breast cancer. <br/><b>Methods</b>: The MEDLINE, EMBASE, Web of science and CBM databases were searchedfor all relevant articles published up to June 20, 2012. Potential associations were assessed with comparisons ofthe total mutation rate (TMR), complete mutation rate (CMR) and partial mutation rate (PMR) in cases andcontrols. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 software. <br/><b>Results</b>: Five studieswere included with a total of 5,165 breast cancer cases and 4,839 healthy controls. Meta-analysis results showedthat mutations of rs2075686 (C>T) and rs6869366 (G>T) in the XRCC4 gene were associated with increasedrisk of breast cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of breast cancer.However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del) and rs3734091 (A>G) polymorphisms ofXRCC4 gene did not appear to have an influence on breast cancer susceptibility. <br/><b>Conclusion</b>: Results from thecurrent meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms of the XRCC4 genemight increase the risk of breast cancer, whereas rs2075685 (G>T) and rs10057194 (A>G) might be protectivefactors.