Cytochrome P450 1A2 (
CYP1A2) is hypothesized to catalyze the activation of arylamines, known human bladder
carcinogens present in cigarette
smoke. The relationship between
CYP1A2 phenotype and
bladder cancer risk was examined in a case-control study involving 519 patients and 514 controls in Shanghai, China. Both
CYP1A2 and N-
acetyltransferase 2 (NAT2) phenotypic status were determined by a
caffeine-based urinary assay. Our study showed that among smokers at urine collection, patients with
bladder cancer had statistically significantly higher
CYP1A2 phenotype scores compared to control subjects (p = 0.001). The odds ratios (95% confidence intervals) of
bladder cancer for the second, third and fourth quartiles of the
CYP1A2 score were 1.31 (0.53-3.28), 2.04 (0.90-4.60) and 2.82 (1.32-6.05), respectively, relative to the lowest quartile (p for trend = 0.003). NAT2 slow acetylation phenotype was associated with a statistically significant 40% increased risk of
bladder cancer, and the relationship was independent of subjects' smoking status. Subjects possessing the NAT2 slow acetylation phenotype and the highest tertile of
CYP1A2 scores showed the highest risk for
bladder cancer. Their odds ratios (95% confidence intervals) was 2.13 (1.24-3.68) relative to their counterparts possessing the NAT2 rapid acetylation phenotype and the lowest tertile of
CYP1A2 scores. The findings of our study demonstrate that
CYP1A2 phenotype may be an important contributing factor in the development of smoking-related
bladder cancer in humans.