Genetic polymorphisms in CYP1A1, CYP1B1, COMT, GSTP1 and NAT2 genes and association with bladder cancer risk in a French cohort.
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.
Fontana
Luc
L
Université Clermont 1, Faculté de Médecine, 28 place Henri Dunant, 63001 Clermont-Ferrand Cedex 01 France. Luc.fontana@u-clermont1.fr
Delort
Laetitia
L
Joumard
Laurie
L
Rabiau
Nadege
N
Bosviel
Remy
R
Satih
Samir
S
Guy
Laurent
L
Boiteux
Jean-Paul
JP
Bignon
Yves-Jean
YJ
Chamoux
Alain
A
Bernard-Gallon
Dominique J
DJ
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*
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