br Conflicts of Interest br Author Contributions

Conflicts of Interest
Author Contributions
Acknowledgements
Introduction Deoxyribonucleic order Merimepodib (DNA) in a normal cell is capable of withstanding internal and external damage to prevent the damage or death of the cell (Alli et al., 2009; Orlow et al., 2008). The direct reversal, base excision, nucleotide excision in the main DNA repair pathways of human beings’ function as restoring lost gene information and maintaining DNA integrity (Rajaraman et al., 2010). Some research studies have already showed that polymorphisms in DNA-repair genes are an integral part of cancer risk, apart from environmental factors, diet, intake of non-steroidal and anti-inflammatory drugs, and endogenous factors (Spitz et al., 2003). At the cellular level, checkpoints activated by the DNA-repair genes can regulate the cell cycle and transcription to make the choice of the damage or the apoptosis (Vispe et al., 2000). In addition, DNA repair-gene is also critical in defending the cellular genome from the risk of environmental factors (Hoeijmakers, 2001). Therefore, making certain of the genetic mechanisms of DNA repair system might take an insight into the pathogenesis of relevant cancers. X-ray repair cross-complementing (XRCC) genes are members of the family of DNA repair system (Dizdaroglu, 2015), which are polymorphic with several non-synonymous polymorphisms, such as Arg194Trp (rs1799782), Arg280His (rs25489), Arg399Gln (rs25487) in XRCC1, Arg188His (rs3218536) polymorphisms in XRCC2, IVS6-14 (rs1799796) and Thr241Met (rs861539) polymorphisms in XRCC3, rs1805377, rs6869366 and rs28360071 polymorphisms in XRCC4 and rs7003908 in XRCC7. To date, plenty of evidences have indicated that more than one hundred proteins encoded by XRCC genes are implicated in four DNA repair pathways, including nucleotide excision repair (NER), base excision repair (BER), double-strand break repair (DSBR) and mismatch repair (MMR), working as tumor suppressors or oncogenes for the sake of participating in tumorigenesis through posting expression regulation of homologous target genes (Liesegang, 2001). Recently, studies have highlighted the ambivalent association between polymorphisms in XRCC genes and risk of urological neoplasms. In the study conducted by Agalliu et al. (2010), they have proved that there was no significant association between XRCC1 polymorphisms (rs1799782, rs25487, rs25489 and rs915927) and prostate cancer (PCa) risk. Consistent with Agalliu et al.\'s conclusion, Lavender et al. (2010) also confirmed that no significant influence of XRCC1-rs25487 polymorphism on PCa risk was identified for African population. While in another population-based case-control dataset, Lan et al. (2006) suggested that XRCC1-rs25487 polymorphism was significantly associated with the development of PCa. Both Matullo (2005) and Nowacka-Zawisza et al. (2015) have not revealed a significant association between XRCC2-rs3218536 polymorphism and urological neoplasms risk in their work, respectively. As for polymorphisms in XRCC3 gene, Wu et al. (2006) indicated that there was no association between XRCC3-rs861539 polymorphism and bladder cancer (BC) risk, while Narter et al. (2009) reported the conflicting results that there was a 4.87-fold protective role of XRCC3 T allele against BC. In 2011, Mandal et al. (2011) conducted a case-control study comprising 192 PCa cases and 224 age-matched healthy controls and obtained a conclusion that XRCC4 promoter-1394 (rs6869366) heterozygote was associated with a lower risk of PCa, a result inconsistent with Chang et al.\'s (2008) work. In addition, Mandal et al. (2010) provided a strong supportive evidence that common sequence variants genotype of XRCC7 gene might increase the risk of PCa. As mentioned above, although many studies have conducted to investigate the associations between one or multiple polymorphism (s) and the risk of urological neoplasms, but there results were not consistent or even contradictory, which was partially due to the heterogeneity within cancer subtypes, the diverse ethnicities of patient cohorts and the small sample sizes. Therefore, we conducted the current updated meta-analysis and systematic review at the aim of precisely determines the association between genetic variants in five XRCC genes and the susceptibility to urological neoplasms.