TY - JOUR
T1 - Genetic polymorphisms of CYP2A6 in a case-control study on 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 - Publisher Copyright:
Copyright © 2016 The Pharmaceutical Society of Japan.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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 allelespecific 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.
AB - 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 allelespecific 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.
KW - Bladder cancer
KW - CYP2A6
KW - Genetic polymorphism
KW - Japanese
KW - Smoking
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U2 - 10.1248/bpb.b15-00604
DO - 10.1248/bpb.b15-00604
M3 - Article
C2 - 26725431
AN - SCOPUS:84954538288
VL - 39
SP - 84
EP - 89
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
SN - 0918-6158
IS - 1
ER -