Document Detail

Genetic polymorphisms of MDM2, cumulative cigarette smoking and nonsmall cell lung cancer risk.
MedLine Citation:
PMID:  17957785     Owner:  NLM     Status:  MEDLINE    
Abnormalities of the tumor suppressor TP53 pathway are critical in the development of many cancers since it regulates cell cycle components and apoptosis. Murine double minute-2 (MDM2) protein is a central node in the p53 pathway and a direct negative regulator of p53. The MDM2 SNP309 (rs2279744) polymorphism increases MDM2 RNA and protein levels, attenuating the p53 pathway. The MDM2 SNP309 polymorphism was investigated in 1,787 Caucasian nonsmall cell lung cancer (NSCLC) patients and 1,360 healthy controls. Cases and controls were analyzed for associations with genotype and adjusted for age, gender, histology and smoking history. There were no overall associations between the MDM2 genotypes and risk of lung cancer (adjusted odds ratios [AORs] = 0.82 [95% confidence interval [CI] = 0.6-1.1] for the T/G genotype and AOR = 1.32 [95% CI = 0.9-2.0] for the G/G genotype). A statistically significant interaction (p = 0.01) was found between smoking and MDM2 genotypes. Consistent with this interaction, stratified analysis by pack-years of smoking demonstrated that the AORs of G/G vs. T/T were 1.56 (1.0-2.7), 1.46 (1.0-2.2), 0.80 (0.5-1.3) and 0.63 (0.4-1.1), respectively, for never, mild (<30 pack-years), moderate (30-57 pack-years) and heavy smokers (>or=58 pack-years). In conclusion, a strong gene-smoking interaction was observed between the MDM2 SNP309 and NSCLC risk.
Geoffrey Liu; Paul Wheatley-Price; Wei Zhou; Sohee Park; Rebecca S Heist; Kofi Asomaning; John C Wain; Thomas J Lynch; Li Su; David C Christiani
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  122     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2007-12-20     Completed Date:  2008-01-17     Revised Date:  2008-02-15    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  915-8     Citation Subset:  IM    
Copyright Information:
(c) 2007 Wiley-Liss, Inc.
Applied Molecular Oncology/Department of Medicine, Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada.
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MeSH Terms
Adenocarcinoma / genetics
Aged, 80 and over
Carcinoma, Large Cell / genetics
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Squamous Cell / genetics
DNA Mutational Analysis
Gene Frequency
Lung Neoplasms / genetics*
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide*
Proto-Oncogene Proteins c-mdm2 / genetics*
Risk Factors
Smoking / adverse effects*
Grant Support
Reg. No./Substance:
EC protein, human; EC Proteins c-mdm2

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