Genetic Association between ERCC2, NBN, RAD51 Gene Variants and Osteosarcoma Risk: a Systematic Review and Meta-Analysis

Abstract

Background: To date, only a few studies have investigated associations between ERCC2, NBN, and RAD51 variants and risk of developing osteosarcoma. In this systematic review and meta-analysis, we focused on clarifying links. Materials and Methods: We systematically searched PubMed, Google Scholar, and ISI web of knowledge databases to identify relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of associations with fixed effect models. Results: No statistical evidence of association was found between ERCC2 rs13181 (G vs. T: OR= 1.224, 95% CI: 0.970-1.545, p= 0.088; GT vs. TT: OR= 1.135, 95% CI: 0.830-1.552, p= 0.428; GG vs. TT: OR= 1.247, 95% CI: 0.738-2.108, p= 0.409; GG+GT vs. TT: OR= 1.174, 95% CI: 0.929-1.484, p= 0.179; GG vs. GT+TT: OR= 1.476, 95% CI: 0.886-2.460, p= 0.135), ERCC2 rs1799793 (GA+AA vs. GG: OR= 1.279, 95% CI: 0.912-1.793, p= 0.154), NBN rs709816 (OR= 1.047, 95% CI: 0.763-1.437, p= 0.775), NBN rs1805794 (OR= 1.126, 95% CI: 0.789-1.608, p= 0.513), RAD51 rs1801320 (OR= 0.977, 95% CI: 0.675-1.416, p= 0.904), RAD51 rs1801321 (TT+GT vs. GG: OR= 1.167, 95% CI: 0.848-1.604, p= 0.343), RAD51 rs12593359 (GG+GT vs. TT: OR= 0.761, 95% CI: 0.759-1.470, p= 0.744) polymorphisms and osteosarcomas. The lack of the original data limited our further evaluation of the adjusted ORs concerning age and gender; however, the previous individual studies results indicated the age- and gender-specific effects of two ERCC2 rs1799793 and NBN rs1805794 variants on osteosarcoma risk. Conclusion: The results suggested a lack of association between the ERCC2 (rs13181 and rs1799793), NBN (rs709816 and rs1805794), and RAD51 (rs1801320, rs1801321, and rs12593359) variants with osteosarcoma risk. Further comprehensive and well-designed studies are required to assess the role for ERCC2, NBN, RAD51 variants in osteosarcoma development more adequately.

Keywords: Osteosarcoma; ERCC2; NBN; RAD51; variant; meta-analysis.

Figure 1

Forest Plot for the Association of the ERCC2, NBN, and RAD51 Gene Polymorphisms and Osteosarcoma. A: ERCC2 rs13181 (dominant: GG+GT vs. TT), B: NBN rs1805794 (dominant: TT+TC vs. CC) and C: RAD51 rs1801321 (GG+GT vs. TT).

Figure 2

Begg’s Funnel Plots of the ERCC2 rs13181 Polymorphism and Osteosarcoma Risk for Publication Bias Test in Dominant Genetic Contrast (GG+GT vs. TT). Each point represents a separate study for the indicated association.