Document Detail


Genetic variants of myeloperoxidase and lung cancer risk.
MedLine Citation:
PMID:  10837005     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cytochrome P450 family of enzymes is responsible for many of the initial metabolic conversions of procarcinogenic compounds in tobacco smoke to reactive metabolites. However, other enzyme-based systems such as myeloperoxidase (MPO) may also be involved in this metabolic process. MPO is a phase I metabolic enzyme that has a polymorphic region upstream of the gene that appears to reduce transcriptional activity. The polymorphic G-->A nucleotide base shift negates the binding region for the general transcription factor SP1. Thus, individuals with the variant allele may be provided with a protective effect due to decreased metabolic conversion of carcinogenic compounds in tobacco smoke. This study has investigated the hypothesis that individuals with the variant allele may be at a reduced risk for lung cancer. Our results demonstrate that the protective effects of the MPO variant allele reduced overall lung cancer risk in Caucasians by 48% (OR = 0.52, 95% CI 0.30-0.90, P = 0.02). There was a 72% protective effect (OR = 0.28, 95% CI 0.12-0.61, P < 0.05) evident in men but not in women. Additionally, in younger individuals (<61 years) there was a statistically significant 72% reduction in risk (OR = 0.28, 95% CI 0. 11-0.69, P < 0.05) but not in older individuals. A protective effect was observed for current smokers (OR = 0.24, 95% CI 0.10-0.58, P < 0. 05) but not in former smokers and those who had never smoked. These data demonstrate that there is a reduction in lung cancer risk associated with a variant allele of MPO that is evident in men, younger individuals and current smokers.
Authors:
M B Schabath; M R Spitz; X Zhang; G L Delclos; X Wu
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Carcinogenesis     Volume:  21     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-08-03     Completed Date:  2000-08-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1163-6     Citation Subset:  IM    
Affiliation:
The University of Texas M.D. Anderson Cancer Center, Department of Epidemiology, Box 189, 1515 Holcombe Boulevard, Houston 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Confidence Intervals
DNA Primers
Female
Genetic Predisposition to Disease
Humans
Lung Neoplasms / enzymology,  genetics*
Male
Odds Ratio
Peroxidase / genetics*
Polymorphism, Genetic
Risk Factors
Smoking
Grant Support
ID/Acronym/Agency:
CA 55769/CA/NCI NIH HHS; CA 68437/CA/NCI NIH HHS; CA 74880/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; EC 1.11.1.7/Peroxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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