The functional MDM2 T309G genetic variant but not P53 Arg72Pro polymorphism is associated with risk of sarcomas: a meta-analysis.
OBJECTIVE
The P53-MDM2 pathway plays a central role in sarcoma pathogenesis. Functional P53 Arg72Pro and MDM2 T309G single-nucleotide polymorphisms (SNP) are considered to have significant effects on risk of sarcomas.


METHODS
Several molecular epidemiology studies have evaluated how these genetic variants are involved in sarcoma development, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically examine the association between these functional SNPs and sarcoma risk.


RESULTS
There are four studies eligible for P53 Arg72Pro SNP (466 sarcoma patients and 552 controls), and three studies for MDM2 T309G SNP (355 sarcoma patients and 645 controls). Pooled odds ratios were appropriately calculated using either fixed-effect model or random-effect model. We did not find a significant association between P53 Arg72Pro polymorphism and sarcoma risk. However, in a stratified analysis, a statistically significant correlation between this SNP and osteosarcoma risk was observed. For MDM2 T309G variant, pooled results from the meta-analysis indicate that carriers of TG and GG genotypes showed a 34% increased risk to develop sarcomas compared to TT carriers.


CONCLUSIONS
These results suggest that the functional MDM2 T309G genetic variant may play a more important role in carcinogenesis of sarcoma.
Department of Orthopedics, Division of Surgery, Chinese PLA General Hospital, Beijing, China.
Xu
X
Cai
Ming
M
Yang
D019943:Amino Acid Substitution; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D012509:Sarcoma / Q000175:diagnosis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2