A comprehensive compilation of data on the association between XRCC3 polymorphisms and thyroid cancer susceptibility

Polymorphisms in the XRCC3 gene, a key component of homologous recombination repair, have been studied for their potential role in thyroid cancer susceptibility. However, published findings remain inconsistent across populations and genetic variants. This meta-analysis aimed to clarify the associations between XRCC3 polymorphisms and thyroid cancer risk, with emphasis on variant- and ethnicity-specific effects.

A systematic search of PubMed, EMBASE, Scopus, CNKI, and other databases up to July 10, 2025 identified case-control studies reporting genotype distributions of XRCC3 polymorphisms in thyroid cancer. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under fixed- or random-effects models. Subgroup analyses by ethnicity, sensitivity tests, and publication bias assessments (Egger's and Begg's tests) were performed.

Twenty-four eligible studies were included: 14 for rs861539, six for rs1799796, and four for rs1799794, comprising 4,502 cases and 6,048 controls. For rs861539, no significant association with thyroid cancer risk was observed in the overall population (T vs. C: OR = 1.089, 95% CI = 0.908-1.306, p = 0.358), with consistent null results across Asian and Caucasian subgroups. For rs1799796, no overall association was detected (G vs. A: OR = 0.970, 95% CI = 0.875-1.075, p = 0.558), but a protective effect emerged in Asian populations (GA vs. AA: OR = 0.835, 95% CI = 0.701-0.995, p = 0.043). For rs1799794, significant associations were found under recessive models (GG vs. AA: OR = 1.371, 95% CI = 1.066-1.762, p = 0.014; GG vs. GA + AA: OR = 1.316, 95% CI = 1.037-1.669, p = 0.024). Considerable heterogeneity was observed (I² = 42.2-93.3%), and eight studies deviated from Hardy-Weinberg equilibrium.

XRCC3 rs1799794 polymorphism is associated with increased thyroid cancer risk, particularly under recessive genetic models. The rs1799796 variant may confer a protective effect in Asian populations, whereas rs861539 shows no significant association. These results highlight population-specific genetic effects and underscore the importance of considering ethnicity in genetic association studies. Further large, well-designed investigations are warranted to confirm these findings and to explore potential gene-environment interactions.