Mutagen sensitivity in patients with familial and non-familial urothelial cell carcinoma.

Due to variation in individual susceptibility, only a fraction of all individuals exposed to environmental carcinogens will develop cancer. Our aim was to assess whether mutagen sensitivity plays a role in developing urothelial cell carcinoma (UCC) and whether this sensitivity is different in familial and non-familial cases. Intrinsic susceptibility was quantified by a mutagen sensitivity assay (mean number of chromatid breaks per cell after damage induction with bleomycin in the late S-G2 phase of the cell cycle). Patients were classified as sporadic (n = 25), familial (2 patients in 1 nuclear family, n = 23) or hereditary (2 patients <60 years or 3 patients in 1 nuclear family, n = 13) and compared with control subjects without a history of cancer. Information on demographic factors, smoking history and family history of UCC was collected by postal questionnaires. Differences in mutagen sensitivity were assessed by ANOVA and logistic regression analysis. Overall, UCC patients showed a higher mutagen sensitivity score compared with control subjects [mean number of chromatid breaks per cell 0.91, 95% confidence interval (CI) 0.84-0.97, and 0.74, 95% CI 0.69-0.79, respectively; p = 0.001). Sporadic and familial patients exhibited the highest susceptibility (0.94, 95% CI 0.82-1.06, and 0.93, 95% CI 0.83-1.03, respectively). Hereditary patients (0.79, 95% CI 0.72-0.86) showed a susceptibility similar to controls. Mutagen sensitivity increases the risk of non-hereditary UCC. The relatively low mutagen sensitivity score among hereditary patients points to a different carcinogenic pathway.