title: Genetic polymorphism of the human cytochrome CYP2A13 in a French population: implication in lung cancer susceptibility.
abstract: The human cytochrome CYP2A13, which is mainly expressed in the respiratory tract, has been shown to be highly efficient in vitro in the metabolism of tobacco-smoke carcinogens and procarcinogens such as 4-methylnitroso-1-(3-pyridyl)-1-butanone (NNK). In order to investigate the extent of CYP2A13 genetic polymorphism in a French Caucasian population of 102 individuals, a screening for sequence variations in the 5'-untranslated and protein encoding regions of its gene was performed using a polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) strategy. Six polymorphisms in the coding region were identified, including two rare missense mutations (C474G or Asp158Glu, G967T or Val323Leu) and one nonsense mutation (Arg101Stop). This deleterious mutation, the most frequent (5%) in our population, presumably encodes a severely truncated protein. The influence of the nonsense mutation in lung cancer susceptibility was examined by PCR-SSCP using peripheral blood DNA from 204 cases of lung cancer and 201 controls. The CYP2A13*7 allele, which harbours the C301T mutation, was present in 2.0% of controls and 3.4% of cases. However, multivariate analysis showed an elevated risk for small cell lung cancer in subjects heterozygous for the null allele (odds ratio OR=9.9; 95% confidence interval CI=1.9-52.2). This increased risk was not linked to other histological types of lung cancer.
authors.affiliation: Equipe d'accueil 2679, Faculté de Médecine de Lille, Pôle Recherche, Lille, France. christelle.cauffiez@caramail.com
authors.forename: Christelle
authors.initials: C
authors.lastname: Cauffiez
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lo-Guidice
authors.forename: Sylvie
authors.initials: S
authors.lastname: Quaranta
authors.forename: Delphine
authors.initials: D
authors.lastname: Allorge
authors.forename: Dany
authors.initials: D
authors.lastname: Chevalier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cenée
authors.forename: Rima
authors.initials: R
authors.lastname: Hamdan
authors.forename: Michel
authors.initials: M
authors.lastname: Lhermitte
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lafitte
authors.forename: Christian
authors.initials: C
authors.lastname: Libersa
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stücker
authors.forename: Franck
authors.initials: F
authors.lastname: Broly
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis / Q000379:methods; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: D018389:Codon, Nonsense; D001189:Aryl Hydrocarbon Hydroxylases; C414206:CYP2A13 protein, human