Using Epidemiology and Genomics to Understand Osteosarcoma Etiology

Table 2

Association studies of single nucleotide polymorphisms and osteosarcoma risk. Abbreviations: SNP: single nucleotide polymorphism; OR: odds ratio; CI: confidence interval.

First Author, Year, Reference	No. cases/no. controls	Study Design	Gene	Main Finding(s)
Patiño-Garcia, 2000, [95]	63/111	Case-Control	Tumor Necrosis Factor-α (TNF)	Evaluated 3 SNPs in the promoter. TNF-α -238G>A was inversely associated with risk (OR 0.17, 95% CI 0.04–0.76, 𝑃=0.0095)
Ruza, 2003, [66]	72/143	Case-Control	Vitamin D Receptor (VDR)	3 SNPs (FokI, ApaI, TaqI) studied. FokI Ff genotype associated with increased risk (OR 1.78, 95% CI 1.0–3.16, 𝑃=0.048)
			Estrogen Receptor (ESR1)	2 variants (Pvu II and XbaI) evaluated were not associated with osteosarcoma
			Collagen 1α1 (COL1A1)	1 variant studied (Msc 1) was not associated with osteosarcoma.
Savage, 2007, [96]	104/74	Hospital-based Case-Control	Tumor Protein p53 (TP53)	12 tag-SNPs in TP53 genotyped. Recessive model noted potential increased risk with rs1642785 (IVS+38C>G; OR 6.7, 95% CI 1.06-41.6, 𝑃=0.04) and rs1042522 (Ex4+119C>G, P72R; OR 7.5, 95% CI 1.2–46.3,𝑃=0.03).
Savage, 2007, [62]	104/74	Hospital-based Case-Control	Insulin-like Growth Factor 2 Receptor (IGF2R)	Evaluated 52 SNPs in 13 growth-related genes. Two linked IGF2R SNPs, rs998075 (Ex16+88G>A) and rs998074 (IVS16+15C>T), associated with increased risk (haplotype OR 2.04, 95% CI 1.29–3.24, 𝑃=0.006).
Koshkina, 2007, [97]	123/510	Case-Control	Fas (TNF receptor superfamily, member 6; FAS)	4 SNPs in Fas studied. Increased risk with exon 3, 18272A>G, most pronounced in non-Hispanic whites (OR 2.3, 95% CI 1.2–4.6, 𝑃=0.014)
Toffoli, 2009, [98]	201/250	Case-Control	Mdm2 p53 binding protein homolog (MDM2)	1 SNP in MDM2 studied, rs2279744 (SNP309T>G), was associated with high-grade osteosarcoma in females
			Tumor Protein p53 (TP53)	1 SNP evaluated, rs1042522 (Ex4+119C>G, P72R), was associated with survival.
Hu, 2010, [99]	168/168	Case-Control	Transforming growth factor beta receptor 1 (TGFBR1)	1 variant evaluated (TGFBR1*6A) was associated with increased susceptibility (OR 4.6, 95% CI 2.3–7.9, 𝑃=0.002)
Mirabello, 2010, [100]	99/1430	Hospital-based Case-Control	8q24 region	Evaluated 214 SNPs, including 9 previously associated with cancer. Strongest association noted at rs896324 in additive model (OR 1.75, 95% CI 1.13–2.69, 𝑃=0.01)