Objective To study the relationship between smoking, a cytochrome P-45
0 gene polymorphism and the development of bladder cancer. Patients an
d methods The study comprised 126 patients with a diagnosis of bladder
cancer from whom a full history was obtained. Genomic DNA was extract
ed from blood sampled from each patient and genotyping of the CYP2D6 l
ocus, the gene responsible for debrisoquine hydroxylase activity, was
performed using a polymerase chain-reaction technique. Besults Of the
126 patients, 78% had a history of smoking. There was a relationship b
etween the number of cigarettes smoked and the grade of the presenting
bladder tumour; heavy smokers developed high-grade disease. There was
a trend for those heterozygous at the CYP2D6 locus and with a history
of smoking to develop more aggressive disease, but this trend did not
reach statistical significance. Conclusion The link between smoking a
nd bladder cancer was confirmed. Furthermore, the grade of the present
ing tumour was related to the 'cigarette-years'. The CYP2D6 genotype m
ay influence the type of bladder cancer that develops in smokers.