Wilkening Stefan, Bermejo Justo Lorenzo, Hemminki Kari
Department of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
Carcinogenesis. 2007 Nov;28(11):2262-7. doi: 10.1093/carcin/bgm191. Epub 2007 Sep 7.
A paper by Bond et al. reported that a single-nucleotide polymorphism (SNP) in the intronic promoter region of the mouse double minute 2 (MDM2) gene (called SNP309) can significantly change the expression of MDM2 and thereby suppress the p53 pathway. Furthermore, it was shown that SNP309 accelerates tumor formation in Li-Fraumeni patients. This initial report aroused the attention of many researchers, which investigated the role of SNP309 for the risk and the onset of cancer in different tissues. To provide a more robust estimate of the effect of this polymorphism on cancer risk, we combined the available genotype data for breast, colorectal and lung cancers. For breast cancer, we combined the data from 11 studies including 5737 cases and 6703 controls. For colorectal cancer, we combined the data from five studies with 1620 cases and 886 controls. For lung cancer, we performed a fixed-effect meta-analysis from seven studies including 4276 cases and 5318 controls. Our results suggest that the SNP309 variant does not have an impact on the risk of breast [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.87-1.08] or colorectal cancers (OR = 0.97, 95% CI = 0.76-1.25). However, the combined estimate of the ORs for lung cancer revealed an increased risk for GG versus TT (OR = 1.27, 95% CI = 1.12-1.44). The data show that SNP309 alone has little or no effect on the risk of common cancers, but it might modify the time of tumor onset and prognosis.
邦德等人的一篇论文报道，小鼠双微体2（MDM2）基因内含子启动子区域的单核苷酸多态性（SNP）（称为SNP309）可显著改变MDM2的表达，从而抑制p53通路。此外，研究表明SNP309会加速李-佛美尼综合征患者的肿瘤形成。这一初步报告引起了许多研究人员的关注，他们研究了SNP309在不同组织中对癌症风险和发病的作用。为了更可靠地估计这种多态性对癌症风险的影响，我们整合了乳腺癌、结直肠癌和肺癌的现有基因型数据。对于乳腺癌，我们整合了11项研究的数据，包括5737例病例和6703例对照。对于结直肠癌，我们整合了5项研究的数据，有1620例病例和886例对照。对于肺癌，我们对7项研究进行了固定效应荟萃分析，包括4276例病例和5318例对照。我们的结果表明，SNP309变体对乳腺癌风险[比值比（OR）=0.97，95%置信区间（CI）=0.87 - 1.08]或结直肠癌风险（OR = 0.97，95%CI = 0.76 - 1.25）没有影响。然而，肺癌OR值的合并估计显示，与TT基因型相比，GG基因型的风险增加（OR = 1.27，95%CI = 1.12 - 1.44）。数据表明，单独的SNP309对常见癌症的风险几乎没有影响，但它可能会改变肿瘤发病时间和预后。
