title: Genetic variants of myeloperoxidase and lung cancer risk.
abstract: 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.affiliation: The University of Texas M.D. Anderson Cancer Center, Department of Epidemiology, Box 189, 1515 Holcombe Boulevard, Houston 77030, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Schabath
authors.forename: M R
authors.initials: MR
authors.lastname: Spitz
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: G L
authors.initials: GL
authors.lastname: Delclos
authors.forename: X
authors.initials: X
authors.lastname: Wu
mesh_terms: D001483:Base Sequence; D016001:Confidence Intervals; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking
chemical_list: D017931:DNA Primers; D009195:Peroxidase