A systematic review and meta-analysis of MDM2 polymorphisms in osteosarcoma susceptibility

Two polymorphisms in the murine double minute 2 (MDM2) gene (rs1690916 and rs2279744) have been associated with the risk of osteosarcoma (OS). When we analyzed these two polymorphisms in two new independents cohorts (Spanish and Slovenian), we found no association. In order to clarify this, we conducted a meta-analysis including six populations, with a total of 246 OS patients and 1,760 controls for rs1690916; and 433 OS patients and 1,959 controls for rs2279744. Pooled odds ratio risks and corresponding 95% CI were estimated to assess the possible associations. Our results showed that these two polymorphisms were not associated with the susceptibility of OS under any genetic model studied. In conclusion, the present meta-analysis indicates that MDM2 rs1690916 and rs2279744 cannot be considered as genetic risk factors for OS susceptibility in the different populations. Therefore, the influence of these two polymorphisms on the risk of OS may be less important than previously suggested. Future studies are needed to confirm these results.

[1]  J. Jazbec,et al.  Homologous Recombination Repair Polymorphisms and the Risk for Osteosarcoma , 2015, Journal of medical biochemistry.

[2]  P. Lønning,et al.  MDM2 promoter SNP285 and SNP309; phylogeny and impact on cancer risk , 2011, Oncotarget.

[3]  R. Hayes,et al.  A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma , 2011, BMC Cancer.

[4]  N. Majkić-Singh,et al.  Integrative Algorithms in Patient Focused Laboratory Medicine , 2013 .

[5]  Vishva M. Dixit,et al.  Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death , 2011, Nature Reviews Molecular Cell Biology.

[6]  Kun Chen,et al.  A Genetic Variant in miR-196a2 Increased Digestive System Cancer Risks: A Meta-Analysis of 15 Case-Control Studies , 2012, PloS one.

[7]  M. Hameed,et al.  Primary malignant bone tumors--recent developments. , 2011, Seminars in diagnostic pathology.

[8]  V. A. Naumov,et al.  Association of FGFR3 and MDM2 Gene Nucleotide Polymorphisms with Bone Tumors , 2012, Bulletin of Experimental Biology and Medicine.

[9]  A. Patiño-García,et al.  Analysis of Polymorphisms of the Vitamin D Receptor, Estrogen Receptor, and Collagen I&agr;1 Genes and Their Relationship With Height in Children With Bone Cancer , 2003, Journal of pediatric hematology/oncology.

[10]  J. Wan,et al.  Association of two polymorphisms rs2910164 in miRNA-146a and rs3746444 in miRNA-499 with rheumatoid arthritis: a meta-analysis. , 2014, Human immunology.

[11]  S. Chanock,et al.  Germ‐line genetic variation of TP53 in osteosarcoma , 2007, Pediatric blood & cancer.

[12]  M. Oren,et al.  Mdm2 promotes the rapid degradation of p53 , 1997, Nature.

[13]  P. Picci,et al.  Effect of TP53 Arg72Pro and MDM2 SNP309 Polymorphisms on the Risk of High-Grade Osteosarcoma Development and Survival , 2009, Clinical Cancer Research.

[14]  Zhan-wang Xu,et al.  Letter regarding Wang et al. entitled “Effects of murine double minute 2 polymorphisms on the risk and survival of osteosarcoma: a systemic review and meta-analysis” , 2014, Tumor Biology.

[15]  David M. Thomas,et al.  Genome-wide Association Study Identifies Two Susceptibility Loci for Osteosarcoma , 2013, Nature Genetics.

[16]  Jingcheng Wang,et al.  Association analysis between genetic variants of MDM2 gene and osteosarcoma susceptibility in Chinese. , 2013, Endocrine journal.

[17]  I. Martín-Guerrero,et al.  Letter regarding Wang et al. entitled “Effects of murine double minute 2 polymorphisms on the risk and survival of osteosarcoma: a systematic review and meta-analysis” , 2014, Tumor Biology.

[18]  L. Shao,et al.  Effects of murine double minute 2 polymorphisms on the risk and survival of osteosarcoma: a systemic review and meta-analysis , 2014, Tumor Biology.

[19]  David M. Thomas,et al.  Comprehensive Mapping of p53 Pathway Alterations Reveals an Apparent Role for Both SNP309 and MDM2 Amplification in Sarcomagenesis , 2010, Clinical Cancer Research.