MDM2 Promoter Polymorphism and Pancreatic Cancer Risk and Prognosis

Details

• Personal Author:
  Asomaning K ; Blaszkowsky L ; Christiani, David C. ; Heist RS ; Kwak EL ; Liu G ; Reid AE ; Ryan DP ; Su L ; Zhai R ; Zhou W ; Zhu AX
• Description:
  Purpose: The mouse double minute 2 homologue (MDM2) -309T/G promoter polymorphism has been associated recently with the development and prognosis of a variety of tumors. The G allele is associated with increased affinity for Sp1 binding and higher MDM2 mRNA and protein levels, leading to diminished tumor suppressor activity of the p53 pathway. We hypothesized that the G allele is also associated with increased risk and worse outcome in pancreatic cancer. Experimental design: We evaluated the association between MDM2 309T/G and the risk of histologically confirmed pancreatic adenocarcinoma at Massachusetts General Hospital using unconditional logistic regression (123 cases and 372 controls). Complete overall survival and progression-free survival data were also available for 109 newly diagnosed patients. Results: The adjusted odds ratios (95% confidence intervals) of pancreatic cancer associated with the MDM2 T/G and G/G genotypes compared with TT were 1.89 (1.20-2.99) and 2.07 (1.03-4.16), respectively (adjusting for age, gender, smoking status, and pack-years of smoking). In Cox proportional hazards model with the wild-type T/T genotype as the reference category and adjusting for stage, treatment, and performance status, both the heterozygous T/G and the homozygous G/G genotypes were associated with decreased progression-free survival [adjusted hazard ratio (95% confidence interval), 1.67 (0.98-2.84) for T/G and 2.28 (1.11-4.71) for G/G] and overall survival [2.64 (1.23-5.67) for T/G and 3.12 (1.22-7.91) for G/G]. Conclusions: The G allele of the MDM2 -309T/G polymorphism is associated with 2- to 3-fold increase risk and progression of pancreatic adenocarcinoma and a corresponding decrease in survival. [Description provided by NIOSH]
• Subjects:
  Aging Genetics Men Mortality Neoplasms Occupational Health Risk Assessment Risk Factors Safety Smokers Women

  More +
• Keywords:
  Adenocarcinomas Age Groups Cancer Genetic Predisposition Humans Mortality Rates Pancreatic-cancer Proteins Risk Factors Smoking Statistical Analysis

  More +
• ISSN:
  1078-0432
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  14
• Issue:
  12
• NIOSHTIC Number:
  nn:20060033
• Citation:
  Clin Cancer Res 2008 Jun; 14(12):4010-4015
• Contact Point Address:
  Geoffrey Liu, 610 UniversityAvenue, Room 7-124,Toronto, Ontario, Canada M5G-2M9
• Email:
  Geoffrey.Liu@uhn.on.ca
• Federal Fiscal Year:
  2008
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Clinical Cancer Research
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e00b6a28fef9f5e2f0f58d5a37fcc03311776ed5a8b307e92f0beae105a1f6a426399c0f1f72f19bb15990866a1a9e3b45a01c5429dc54fb9b8356a97bf63dc7
• Download URL:
  https://stacks.cdc.gov/view/cdc/224069/cdc_224069_DS1.pdf
• File Type:
  [PDF - 201.63 KB ]