title: MDM2 polymorphism, survival, and histology in early-stage non-small-cell lung cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Rebecca Suk
authors.initials: RS
authors.lastname: Heist
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Lucian R
authors.initials: LR
authors.lastname: Chirieac
authors.forename: Thea
authors.initials: T
authors.lastname: Cogan-Drew
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: John C
authors.initials: JC
authors.lastname: Wain
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis / Q000235:genetics*
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2