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Genetic polymorphisms of MDM2, cumulative cigarette smoking and nonsmall cell lung cancer risk

Geoffrey Liu1, Paul Wheatley-Price, Wei Zhou

  • 1Applied Molecular Oncology/Department of Medicine, Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada. geoffrey.liu@uhn.on.ca

International Journal of Cancer
|October 25, 2007
PubMed

Insights

The MDM2 SNP309 gene variant does not directly increase lung cancer risk. However, it significantly interacts with smoking habits, altering cancer risk based on smoking intensity.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The tumor suppressor TP53 pathway is crucial for cancer development, regulating cell cycle and apoptosis.
  • Murine double minute-2 (MDM2) protein negatively regulates p53, a key tumor suppressor.
  • The MDM2 SNP309 polymorphism elevates MDM2 levels, potentially weakening the p53 pathway.

Purpose of the Study:

  • To investigate the association between the MDM2 SNP309 polymorphism and nonsmall cell lung cancer (NSCLC) risk in Caucasians.
  • To explore potential interactions between MDM2 genotypes and smoking history in relation to NSCLC risk.

Main Methods:

  • A case-control study involving 1,787 NSCLC patients and 1,360 healthy controls.
  • Genotyping for MDM2 SNP309 (rs2279744) was performed.
  • Statistical analyses adjusted for age, gender, histology, and smoking history, including pack-years.

Main Results:

  • No overall association was found between MDM2 genotypes and NSCLC risk.
  • A significant interaction (p=0.01) was observed between MDM2 genotypes and smoking.
  • Stratified analysis revealed that the G/G genotype increased lung cancer risk in never and light smokers but decreased it in moderate and heavy smokers compared to T/T.

Conclusions:

  • The MDM2 SNP309 polymorphism alone does not appear to influence NSCLC risk.
  • A significant gene-smoking interaction exists, where the risk associated with MDM2 SNP309 varies considerably with smoking pack-years.

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