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.
Department of Epidemiology and Biostatistics and Ministry of Education Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Jing
J
Dong
Binhui
B
Ren
Zhibin
Z
Hu
Jiaping
J
Chen
Lingmin
L
Hu
Juncheng
J
Dai
Guangfu
G
Jin
Lin
L
Xu
Hongbing
H
Shen
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2