Genetic polymorphism of the human cytochrome CYP2A13 in a French population: implication in lung cancer susceptibility.
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.
Cauffiez
Christelle
C
Equipe d'accueil 2679, Faculté de Médecine de Lille, Pôle Recherche, Lille, France. christelle.cauffiez@caramail.com
Lo-Guidice
Jean-Marc
JM
Quaranta
Sylvie
S
Allorge
Delphine
D
Chevalier
Dany
D
Cenée
Sylvie
S
Hamdan
Rima
R
Lhermitte
Michel
M
Lafitte
Jean-Jacques
JJ
Libersa
Christian
C
Colombel
Jean-Frédéric
JF
Stücker
Isabelle
I
Broly
Franck
F
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
D018389:Codon, Nonsense; D001189:Aryl Hydrocarbon Hydroxylases; C414206:CYP2A13 protein, human