Genetic Polymorphisms of <i>CYP2A6</i> in a Case-Control Study on Bladder Cancer in Japanese Smokers
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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 <i>CYP2A6</i> (<i>CYP2A6</i>*<i>4</i>) 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 <i>CYP2A6</i> 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 <i>CYP2A6</i> polymorphisms and the risk of bladder cancer. Determination of <i>CYP2A6</i> genotypes was carried out by amplifying each exon of <i>CYP2A6</i> using polymerase chain reaction (PCR) and Sanger sequencing. The <i>CYP2A6</i>*<i>4</i> allele was identified by an allele-specific PCR assay. Bladder cancer risk was evaluated using the activity score (AS) system based on <i>CYP2A6</i> 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 <i>CYP2A6</i> genotypes and the risk of bladder cancer.
- Biological and Pharmaceutical Bulletin
Biological and Pharmaceutical Bulletin 39(1), 84-89, 2016
The Pharmaceutical Society of Japan