Systematic meta-analysis of genetic variants associated with osteosarcoma susceptibility

In the past decade, accumulated evidence has suggested that genetic variation is related to the pathogenesis of osteosarcoma. Although there are a large number of studies on the association between genetic variation and osteosarcoma, their results are inconsistent. To clarify these findings, we performed a systematic meta-analysis using allelic contrasts for each gene-specific single nucleotide variants with all available data in the field of osteosarcoma.

The literature search for relevant studies was conducted in PubMed, Embase, and Cochrane databases. Pooled ORs and 95% CI values were calculated by the random-effects model using the Comprehensive Meta-analysis version 2.0 software package. Heterogeneity between studies was examined by the Cochran's Q-test.

The 32 genome-wide case-control population-based studies, involving 15,336 study subjects (6924 cases and 8412 controls), were included in this meta-analysis. We analyzed 24 single nucleotide variants (SNVs) in 14 genes. We identified 12 SNVs in CTLA-4, IL-8, MDM2, PRCKG, RECQL5, TNF-a, TP53, XRCC3, and VEGF that correlated with osteosarcoma susceptibility. The average pooled odds ratio for the 9 risk alleles was 2.082 (range: 1.585 to 3.262). These included CTLA-4 rs231775, CTLA-4 rs5742909, PRCKG rs454006, RECQL5 rs820196, TNF-α rs1800629, TP53 rs1042522, XRCC3 rs861539, VEGF rs699947, and VEGF rs3025039. The average pooled odds ratio for the 3 protective alleles, IL-8 rs4073, MDM2 rs1690916, and VEGF rs2010963, was 0.606 (range: 0.510-0.719). Publication bias was not observed among the studies reporting positively correlated SNVs. The pooled odds ratios for the SNVs that correlated with osteosarcoma risk showed homogeneity.

Our results provide powerful information for tracking the most viable gene candidates. Further studies with larger multiethnicity populations and investigations of the potential biological roles of these genetic variants in osteosarcoma should be conducted.