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Genetic polymorphism of the human cytochrome CYP2A13 in a French population: implication in lung cancer susceptibility
Genetic polymorphism of the human cytochrome CYP2A13 in a French population: implication in lung cancer susceptibility
- Source :
- Biochemical and biophysical research communications. 317(2)
- Publication Year :
- 2004
-
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.
- Subjects :
- Male
Lung Neoplasms
Population
Nonsense mutation
DNA Mutational Analysis
Biophysics
Mutation, Missense
Biology
Biochemistry
Risk Assessment
White People
Risk Factors
medicine
Missense mutation
Humans
Genetic Predisposition to Disease
Genetic Testing
Allele
education
Lung cancer
Molecular Biology
Genetics
education.field_of_study
Polymorphism, Genetic
Cell Biology
Middle Aged
medicine.disease
Molecular biology
Null allele
Lung cancer susceptibility
CYP2A13
Codon, Nonsense
Case-Control Studies
Aryl Hydrocarbon Hydroxylases
France
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 317
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....c8c5271954399b82e56ec651a06c4240