MDM2 polymorphism, survival, and histology in early-stage non-small-cell lung cancer

J Clin Oncol. 2007 Jun 1;25(16):2243-7. doi: 10.1200/JCO.2006.08.8914.

Abstract

Purpose: MDM2 is a negative regulator of p53. The MDM2 309T/G polymorphism has been associated with differential MDM2 expression levels and inhibition of the p53 pathway. We hypothesized that the MDM2 G/G genotype may be associated with worse survival outcomes in lung cancer, especially in squamous cell cancers where p53 abnormalities are more common.

Patients and methods: We evaluated the relationship between MDM2 polymorphism status and overall survival (OS) among patients with early-stage non-small-cell lung cancer (NSCLC) treated with surgical resection at Massachusetts General Hospital from 1992 to 2000. Kaplan-Meier methods and the log-rank test were used to compare survival by polymorphism status. Cox proportional hazards models were used to adjust for possible confounding variables.

Results: There were 383 patients in the analysis. In the early-stage population as a whole, the G/G genotype seemed to be associated with worse OS on adjusted analysis (adjusted hazard ratio = 1.57; 95% CI, 1.03 to 2.40; P = .04). Among patients with squamous histology, OS was significantly worse among those with the G/G genotype (P = .0001 by log-rank test), with 5-year survival rates among the genotypes of 59% for T/T, 53% for T/G, and 7% for G/G.

Conclusion: Our findings suggest that the G/G genotype of the MDM2 polymorphism is associated with worse OS among early-stage NSCLC patients, particularly those with squamous cell histology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Genotype
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Proto-Oncogene Proteins c-mdm2 / analysis
  • Proto-Oncogene Proteins c-mdm2 / genetics*

Substances

  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2