| Genetic polymorphisms of MDM2, cumulative cigarette smoking and nonsmall cell lung cancer risk. | |
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MedLine Citation:
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PMID: 17957785 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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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:
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Created Date: 2007-12-20 Completed Date: 2008-01-17 Revised Date: 2008-02-15 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 915-8 Citation Subset: IM |
Copyright Information:
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(c) 2007 Wiley-Liss, Inc. |
Affiliation:
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Applied Molecular Oncology/Department of Medicine, Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada. geoffrey.liu@uhn.on.ca |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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genetics Adult Aged Aged, 80 and over Carcinoma, Large Cell / genetics Carcinoma, Non-Small-Cell Lung / genetics* Carcinoma, Squamous Cell / genetics DNA Mutational Analysis Female Gene Frequency Genotype Humans Lung Neoplasms / genetics* Male Middle Aged Odds Ratio Polymorphism, Single Nucleotide* Prognosis Proto-Oncogene Proteins c-mdm2 / genetics* Risk Factors Smoking / adverse effects* |
| Grant Support | |
ID/Acronym/Agency:
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CA074386/CA/NCI NIH HHS; CA090578/CA/NCI NIH HHS; ES/CA 06409/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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