title: Point: myeloperoxidase -463G --> a polymorphism and lung cancer risk.
abstract: Myeloperoxidase (MPO) is released from neutrophils in lung tissue in response to exposure to various pulmonary insults, including tobacco smoking. This enzyme is involved in the activation of an intermediate metabolite of benzo(a)pyrene to the highly reactive benzo(a)pyrene diol epoxide. A (-463)G --> A polymorphism in the promoter region of the MPO gene has been identified. The A allele is associated with a decreased transcriptional activity attributable to the disruption of a SP1-binding site. We therefore examined whether carriers of the A allele may be at reduced risk of lung cancer in a case-control study of 150 cases and 172 control individuals, all Caucasian smokers. Relative to subjects with the MPO G/G genotype, a significant decreased risk of lung cancer was found for carriers of the G/A genotype [odds ratio (OR) = 0.5, 95% confidence interval (CI): 0.29-0.88]. A reduction in risk, although not statistically significant, was also observed for subjects with the A/A genotype (OR = 0.84, 95% CI: 0.31-2.32). The lung cancer risk for carriers of one or two copies of the A allele was 0.55 (95% CI: 0.33-0.93). Because of the low prevalence of the A/A genotype, we also performed a meta-analysis of 2686 lung cancer cases and 3325 controls. The summary OR suggested a slight protective effect of the A/A genotype (OR = 0.86, 95% CI: 0.67-1.1), but this finding was strongly influenced by the results of a single large study. The meta-analysis restricted to studies comprising a homogeneous set yielded an OR of 0.68 (95% CI: 0.5-0.93). However, because of the heterogeneity in individual study results, additional large case-control studies are warranted to provide a more definitive conclusion.
authors.affiliation: Unit of Cancer Epidemiology (INSERM U521), Gustave-Roussy Institute, 94805 Villejuif, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Feyler
authors.forename: Anu
authors.initials: A
authors.lastname: Voho
authors.forename: Christine
authors.initials: C
authors.lastname: Bouchardy
authors.forename: Katja
authors.initials: K
authors.lastname: Kuokkanen
authors.forename: Pierre
authors.initials: P
authors.lastname: Dayer
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
mesh_terms: D000368:Aged; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D009195:Peroxidase / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D015996:Survival Rate
chemical_list: D009195:Peroxidase