Department of Orthopedics, Division of Surgery, Chinese PLA General Hospital, Beijing, China.
J Cancer Res Clin Oncol. 2012 Apr;138(4):555-61. doi: 10.1007/s00432-011-1124-8. Epub 2011 Dec 29.
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.
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.
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.
These results suggest that the functional MDM2 T309G genetic variant may play a more important role in carcinogenesis of sarcoma.
P53-MDM2 途径在肉瘤发病机制中起着核心作用。功能性 P53 Arg72Pro 和 MDM2 T309G 单核苷酸多态性（SNP）被认为对肉瘤的风险有显著影响。
已有多项分子流行病学研究评估了这些遗传变异如何参与肉瘤的发生，但结论不一致。因此，我们进行了这项荟萃分析，以系统地检查这些功能性 SNP 与肉瘤风险之间的关联。
有四项研究符合 P53 Arg72Pro SNP（466 名肉瘤患者和 552 名对照者）的纳入标准，有三项研究符合 MDM2 T309G SNP（355 名肉瘤患者和 645 名对照者）的纳入标准。使用固定效应模型或随机效应模型适当计算了汇总优势比。我们没有发现 P53 Arg72Pro 多态性与肉瘤风险之间存在显著关联。然而，在分层分析中，发现该 SNP 与骨肉瘤风险之间存在统计学上的显著相关性。对于 MDM2 T309G 变体，荟萃分析的汇总结果表明，与 TT 携带者相比，TG 和 GG 基因型携带者发生肉瘤的风险增加了 34%。
这些结果表明，功能性 MDM2 T309G 遗传变异可能在肉瘤的致癌作用中发挥更重要的作用。
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