MDM2 SNP309 Contributes to Non-Small Cell Lung Cancer Survival in Chinese

Murine double minute 2 (MDM2) is a negative regulator of the tumor suppressor gene p53. Single nucleotide polymorphisms in MDM2 and p53 can affect patient's response to chemotherapy as well as overall survival of many cancers. This study aimed to assess the associations between polymorphisms in MDM2 and p53 and survival of non-small cell lung cancer (NSCLC) patients in Chinese. We selected and genotyped both potentially functional SNPs and tagging SNPs in MDM2 and p53 using Illumina Golden Gate platform in a cohort of 568 NSCLC patients. Associations between genotypes and NSCLC median survival time (MST) were assessed using the Kaplan-Meier method. Cox proportional hazard models were performed with the adjustment for age, stage, smoking, histology, surgical operation, and chemo-or radiotherapy status. We found that the MDM2 SNP309 (rs2279744) GT/TT genotypes were associated with a significantly worse survival (MST: 23.0 mo for GT/TT vs. 33.0 mo for GG; log-rank P = 0.028). In the multivariate Cox regression analyses, the MDM2 SNP309GT/TT genotypes were associated with a 1.42-fold [HR = 1.42,95% confidence interval (CI), 1.09-1.84] increased risk of death of NSCLC, compared with SNP309GG genotype. MDM2 SNP309 may be used as one of the candidate biomarkers to predict NSCLC survival. (C) 2011 Wiley-Liss, Inc.