title: CYP2A13 Genetic Polymorphisms in Relation to the Risk of Bladder Cancer in Japanese Smokers.
abstract: Tobacco-specific nitrosamines including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), which can be activated by the metabolic enzyme CYP2A13, are potent procarcinogens. Smoking plays a role in carcinogenesis in the human bladder, which expresses CYP2A13 at a relatively high level. Numerous genetic polymorphisms of CYP2A13 causing amino acid substitution might reduce CYP2A13 metabolic activity toward NNK and NNN, resulting in decreased susceptibility to bladder cancer. The aim of this study was to reveal any association between bladder cancer development and CYP2A13 genetic polymorphisms in Japanese smokers. The CYP2A13 genotype of each subject (163 bladder cancer patients and 161 controls) was determined by next-generation sequencing (NGS) of the full CYP2A13 gene. All samples were genotyped for five CYP2A13 variant alleles (CYP2A13*2, *3, *4, *6, *7). Based on biological logistic regression, the odds ratio (95% confidence interval) for the CYP2A13*1/*2 genotype was 0.34 (0.17-0.69). Thus, CYP2A13 genetic polymorphisms might play important roles in the development of bladder cancer in Japanese smokers.
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kumondai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hosono
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Orikasa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takayama
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking / Q000453:epidemiology / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C414206:CYP2A13 protein, human