Journal of Urology 113(5): 629-635, 1975.
McCullough DL, Lamma DL, McLaughlin AP III, et al.
A family in which transitional cell carcinoma of the bladder was found in 6 of 34 members who lived beyond age 30 is described; possible etiologic factors, including heredity, carcinogen-exposure, immunologic competence, and tryptophan metabolism, are also evaluated. A geneology involving 185 family members in six generations was created. Medical histories were obtained and documented where possible, and evidence of exposure to carcinogens was recorded. Histological sections showing transitional cell tumors from five patients were examined. No evidence was found of common exposure to carcinogens; 2 of the 6 had no exposure to tobacco. Three cases occurred among brothers in the first generation; two of the second generation patients were sons of one of these brothers. A daughter of another brother was affected. Screening evaluations were performed on the immediate relatives of the second generation brother pair. In this group no additional tumors were found; urinary cytology and urinalysis were normal. Tryptophan metabolism was normal in all family members, including one of the patients who has had continued recurrences of transitional cell carcinoma. Histocompatibility antigen was compatible with the family relationships reported. Immunologic competence was normal in all unaffected family members, except a daughter of the patient with recurring carcinoma who showed impaired lymphocyte reactivity on repeated testing. Although several previous studies attempting to relate bladder cancer to heredity have failed to demonstrate any statistically significant correlation, the transmission of bladder carcinoma in this family is compatible with an autosomal dominate trait. Since the parent generation was unaffected, the authors suggest that either a mutation occurred in one of the parents or that one parent carried the mutation without expressing it. The mutation passed to approximately half of the offspring, with a high incidence of physical expression. The gene may not be entirely specific, as associated malignancies in patients and other carcinomas in unaffected relations occurred in those who might be expected to have inherited the genetic mutation.
Rheinische Friedrich- Wilhelms- Universität Bonn