TY - JOUR
T1 - CYP2A13 genetic polymorphisms in relation to the risk of bladder cancer in Japanese smokers
AU - Kumondai, Masaki
AU - Hosono, Hiroki
AU - Orikasa, Kazuhiko
AU - Arai, Yoichi
AU - Arai, Tomio
AU - Sugimura, Haruhiko
AU - Ozono, Seiichiro
AU - Sugiyama, Takayuki
AU - Takayama, Tatsuya
AU - Sasaki, Takamitsu
AU - Hirasawa, Noriyasu
AU - Hiratsuka, Masahiro
N1 - Funding Information:
This study was supported by Grants from the Smoking Research Foundation, Ministry of Health, Labour and Welfare (MHLW) of Japan ("Initiative to facilitate the development of innovative drugs, medical devices, and cellular and tissue-based products"), the Japan Research Foundation for Clinical Pharmacology, the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan S001, and Japan Agency for Medical Research and Development (AMED).
Publisher Copyright:
© 2016 The Pharmaceutical Society of Japan.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Bladder cancer
KW - CYP2A13
KW - Genetic polymorphism
KW - Japanese
KW - Smoking
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U2 - 10.1248/bpb.b16-00422
DO - 10.1248/bpb.b16-00422
M3 - Article
C2 - 27725446
AN - SCOPUS:84989339167
SN - 0918-6158
VL - 39
SP - 1683
EP - 1686
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 10
ER -
