Association between XRCC3 rs861539 Polymorphism and the Risk of Ovarian Cancer: Meta-Analysis and Trial Sequential Analysis

Background: Current studies on the relationship between XRCC3 rs861539 polymorphism and ovarian cancer risk have been inconsistent. Therefore, we performed a meta-analysis to explore their association.

Methods: Six electronic databases (PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and China Wanfang Database) were searched for relevant studies published before December 2021. Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias analysis were performed using Stata software 16.0. Trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software.

Results: A total of 12 studies were included in 9 literatures, comprising 4,634 cases of ovarian cancer and 7,381 controls. After Bonferroni correction, the meta-analysis showed an association between XRCC3 rs861539 polymorphism and ovarian cancer risk in the heterozygote model and the dominant model (GA vs. GG: OR = 0.88, 95%CI = 0.81-0.96, P = 0.003; GG vs. GA+AA: OR = 0.89, 95%CI = 0.82-0.96, P = 0.004). In an ethnically stratified subgroup analysis, XRCC3 rs861539 was shown to reduce the risk of ovarian cancer in Caucasian in the heterozygote model and the dominant model (GA vs. GG: OR = 0.88, 95%CI = 0.81-0.96, P = 0.004; GG vs. GA+AA: OR = 0.88, 95%CI = 0.81-0.96, P = 0.004). In the control source and detection method stratified subgroup analysis, hospital-based studies and PCR-RFLP-based studies were found to increase ovarian cancer risk (GG vs. AA: OR = 1.30, 95%CI = 1.05-1.62, P = 0.016; GG vs. AA: OR = 1.31, 95%CI = 1.06-1.62, P = 0.013).

Conclusion: This meta-analysis showed a significant association between XRCC3 rs861539 polymorphism and ovarian cancer risk, especially in Caucasians. Large-scale multicenter case-control studies in more different regions will be needed in the future.