Polymorphism and smoking in bladder carcinogenesis

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Abstract
To study the relationship between smoking, a cytochrome P-450 gene polymorphism and the development of bladder cancer. The study comprised 126 patients with a diagnosis of bladder cancer from whom a full history was obtained. Genomic DNA was extracted from blood sampled from each patient and genotyping of the CYP2D6 locus, the gene responsible for debrisoquine hydroxylase activity, was performed using a polymerase chain-reaction technique. Of the 126 patients, 78% had a history of smoking. There was a relationship between 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. The link between smoking and bladder cancer was confirmed. Furthermore, the grade of the presenting tumour was related to the 'cigarette-years'. The CYP2D6 genotype may influence the type of bladder cancer that develops in smokers.

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