MDM2 SNP309 and cancer risk: a combined analysis

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.