BACKGROUND: DNA repair mechanisms, particularly RAD51-mediated homologous recombination repair, play a crucial role in breast cancer development, with the rs1801320 (135G >
C) polymorphism showing conflicting associations across studies. This meta-analysis aimed to assess the relationship between RAD51 rs1801320 polymorphism and breast cancer susceptibility. METHOD: We systematically searched PubMed and Web of Science databases through August 15, 2024, and included 16 case-control studies comprising 4743 breast cancer cases and 4448 controls, analyzing various genetic models using R Studio. RESULTS: Our results revealed significant associations in several genetic models: the allele contrast model (C vs. G) showed an increased risk (OR = 1.37, 95% CI: 1.04-1.80, p = 0.0249. The recessive model (CC vs. CG + GG) demonstrated a strong risk association (OR = 2.68, 95% CI: 1.55-4.61, p = 0.00038), while the dominant model (CC + CG vs. GG) showed no significant association (OR = 1.12, 95% CI: 0.98-1.28, p = 0.1037). Pairwise comparisons revealed the CC genotype as a substantial risk factor, particularly in CC vs. GG (OR = 2.31, 95% CI: 1.58-3.37, p = 0.00001) and CC vs. CG (OR = 2.97, 95% CI: 1.53-5.77, p = 0.00128) comparisons. Most models showed moderate to high heterogeneity (I CONCLUSION: This comprehensive meta-analysis is larger than previous studies and provides robust evidence that the RAD51 rs1801320 CC genotype significantly increases breast cancer risk, particularly in recessive and homozygous comparison models, suggesting potential implications for cancer risk assessment and therapeutic strategies targeting DNA repair mechanisms.