title: Genetic polymorphisms in CYP1A1, CYP1B1, COMT, GSTP1 and NAT2 genes and association with bladder cancer risk in a French cohort.
abstract: Tobacco smoking and environmental exposures are the main known risk factors for bladder cancer (BC) via exposure to chemical carcinogens. Genetic differences in the metabolism of chemicals have been suggested to be associated with individual susceptibility to BC. Polymorphisms in genes coding to metabolising enzymes, resulting in variation of carcinogen detoxification efficiency, may therefore change the response of individuals to chemical carcinogens and be associated with an increased BC risk.
  
  
  METHODS
  The aim of the study was to investigate the association between functional polymorphisms in CYP1A1, CYP1B1, COMT, GSTP1 and NAT2 genes and BC risk, through a hospital-based case-control study. The genotyping of 11 Single Nucleotide Polymorphisms (SNPs) was carried out on DNA of 51 bladder cancer male patients and 45 male controls. The technique of MGB (Minor Groove Binder) probes that utilize allelic discrimination with the Taqman(R) method was used.
  
  
  RESULTS
  Individuals with NAT2 slow acetylator genotypes had a significant increase in risk of BC compared to individuals with NAT2 rapid acetylators (OR adjusted for smoking status=2.70; 95% CI, 1.10-6.61). GSTP1 Ile(105)Val variants (deletion of one - Ile/Val- and two -Val/Val-, null genotype- copies) showed a marginal increased risk of BC with OR adjusted for smoking status of 2.27 (95% CI, 0.97-5.31) compared to individuals carrying wild-type genotype (Ile/Ile). No statistically significant effects on BC risk with CYP1A1, CYP11B1 and COMT genotypes were observed.
  
  
  CONCLUSIONS
  The results are consistent with previous literature among Caucasian populations.
authors.affiliation: Université Clermont 1, Faculté de Médecine, 28 place Henri Dunant, 63001 Clermont-Ferrand Cedex 01 France. Luc.fontana@u-clermont1.fr
authors.forename: Luc
authors.initials: L
authors.lastname: Fontana
authors.forename: Laetitia
authors.initials: L
authors.lastname: Delort
authors.forename: Laurie
authors.initials: L
authors.lastname: Joumard
authors.forename: Nadege
authors.initials: N
authors.lastname: Rabiau
authors.forename: Remy
authors.initials: R
authors.lastname: Bosviel
authors.forename: Samir
authors.initials: S
authors.lastname: Satih
authors.forename: Laurent
authors.initials: L
authors.lastname: Guy
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Boiteux
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.forename: Alain
authors.initials: A
authors.lastname: Chamoux
authors.forename: Dominique J
authors.initials: DJ
authors.lastname: Bernard-Gallon
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D015331:Cohort Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D017931:DNA Primers; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D017931:DNA Primers; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D002394:Catechol O-Methyltransferase; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D005982:Glutathione Transferase