Department of Epidemiology and Biostatistics and Ministry of Education Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Mol Carcinog. 2011 Jun;50(6):433-8. doi: 10.1002/mc.20727. Epub 2011 Jan 25.
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.
鼠双微体 2（MDM2）是肿瘤抑制基因 p53 的负调控因子。MDM2 和 p53 的单核苷酸多态性可影响患者对化疗的反应以及多种癌症的总生存率。本研究旨在评估中国非小细胞肺癌（NSCLC）患者中 MDM2 和 p53 多态性与生存的相关性。我们使用 Illumina Golden Gate 平台在 568 例 NSCLC 患者的队列中选择并对 MDM2 和 p53 中的潜在功能 SNP 和标签 SNP 进行基因分型。使用 Kaplan-Meier 方法评估基因型与 NSCLC 中位生存时间（MST）之间的关系。使用 Cox 比例风险模型进行调整，包括年龄、分期、吸烟状况、组织学、手术、化疗或放疗状况。我们发现 MDM2 SNP309（rs2279744）GT/TT 基因型与生存显著相关（MST：GT/TT 为 23.0 个月，GG 为 33.0 个月；log-rank P=0.028）。在多变量 Cox 回归分析中，与 SNP309GG 基因型相比，MDM2 SNP309GT/TT 基因型与 NSCLC 死亡风险增加 1.42 倍[风险比（HR）=1.42，95%置信区间（CI）1.09-1.84]。MDM2 SNP309 可作为预测 NSCLC 生存的候选生物标志物之一。
