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

Due to variation in individual susceptibility, only a fraction of all indiv iduals exposed to environmental carcinogens will develop cancer. Our aim wa s to assess whether mutagen sensitivity plays a role in developing urotheli al cell carcinoma (UCC) and whether this sensitivity is different in famili al and non-familial cases. Intrinsic susceptibility was quantified by a mut agen sensitivity assay (mean number of chromatid breaks per cell after dama ge induction with bleomycin in the late S-G(2) phase of the cell cycle). Pa tients were classified as sporadic (n = 25), familial (2 patients in 1 nucl ear family, n = 23) or hereditary (2 patients <60 years or 3 patients in I nuclear family, n = 13) and compared with control subjects without a histor y of cancer. Information on demographic factors, smoking history and family history of UCC was collected by postal questionnaires. Differences in muta gen sensitivity were assessed by ANOVA and logistic regression analysis. Ov erall, UCC patients showed a higher mutagen sensitivity score compared with control subjects [mean number of chromatid breaks per cell 0.91, 95% confi dence 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 susceptibili ty (0.94, 95% CI 0.82-1.06, and 0.93, 95% CI 0.83-1.03, respectively). Here ditary patients (0.79, 95% CI 0.72-0.86) showed a susceptibility similar to controls. Mutagen sensitivity increases the risk of non-hereditary UCC. Th e relatively low mutagen sensitivity score among hereditary patients points to a different carcinogenic pathway. Int. J. Cancer 88:493-496, 2000. (C) 2000 Wiley-Liss, Inc.