Abstract
The effects and underlying mechanism of XRCC3 rs861539 on the risk of ovarian cancer (OC) are still unclear. Therefore, a meta-analysis of 10 studies containing 6,375 OC cases and 10,204 controls was performed for this topic. Compared with GG genotype, GA + AA genotypes could significantly decrease the OC risk, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were 0.89 (0.83-0.95) and P=0.001, and 0.88 (0.82-0.95) and P=0.001 under the dominant and heterozygous genetic models. Compared with G allele, rs861539 A could significantly reduce the OC risk, OR and its corresponding 95% CI was 0.94 (0.89-0.98) and P=0.007. By subgroup analysis in ethnicity, protective effects on OC risk in Caucasians were observed (the dominant model: OR = 0.88, 95% CI = 0.82-0.94, P<0.001; the heterozygous model: OR = 0.87, 95% CI = 0.81-0.94, P<0.001; the allelic model: OR = 0.93, 95% CI = 0.88-0.97, P=0.003; the homozygous model: OR = 0.89, 95% CI = 0.80-0.98, P=0.024). The authenticity of positive association findings was further confirmed by trial sequential analysis (TSA) and false-positive report probability (FPRP) analysis. The subsequent functional analysis revealed that rs861539 could regulate the post-transcriptional expression of XRCC3 by changing the activity of putative splice sites and types of splicing factors. rs861539 also may act as an expression Quantitative Trait Loci (eQTL) affecting the expression of genes such as XRCC3, MARK3, APOPT1, etc., and has an impact on the structure of XRCC3.