title: Genetic Polymorphisms of CYP2A6 in a Case-Control Study on Bladder Cancer in Japanese Smokers.
abstract: Several of the procarcinogens inhaled in tobacco smoke, the primary risk factor for bladder cancer, are activated by CYP2A6. The association between the whole-gene deletion of CYP2A6 (CYP2A6*4) and a reduced risk of bladder cancer was suggested in Chinese Han smokers. However, there is no evidence for association between the risk of bladder cancer and CYP2A6 genotypes in the Japanese population. Using genomic DNA from smokers of the Japanese population (163 bladder cancer patients and 116 controls), we conducted a case-control study to assess the association between CYP2A6 polymorphisms and the risk of bladder cancer. Determination of CYP2A6 genotypes was carried out by amplifying each exon of CYP2A6 using polymerase chain reaction (PCR) and Sanger sequencing. The CYP2A6*4 allele was identified by an allele-specific PCR assay. Bladder cancer risk was evaluated using the activity score (AS) system based on CYP2A6 genotypes. The odds ratios (95% confidence interval) for the AS 0, AS 0.5, AS 1.0, and AS 1.5 groups were 0.46 (0.12-1.83), 0.43 (0.15-1.25), 0.86 (0.40-1.86), and 1.36 (0.60-3.06), respectively. In conclusion, although decreased CYP2A6 AS tended to reduce the risk of bladder cancer in Japanese smokers, no significant association was recognized in this population. However, given the relatively small size of the sample, further study is required to conclude the lack of a statistically significant association between CYP2A6 genotypes and the risk of bladder cancer.
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; D044466:Asian People; D016022:Case-Control Studies; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6