Cancer families: human models of susceptibility to neoplasia--the Richard and Hinda Rosenthal Foundation Award lecture.

Members of cancer families are at exceptionally high risk and can be studied as human models of cancer susceptibility. These patients represent rare "experiments of nature" that can reveal new insights into carcinogenic processes. We use clinical observations to identify the high risk patient, epidemiological studies to quantitate the excess risk, and laboratory investigations to examine the biological basis of susceptibility. We have uncovered a series of new family cancer syndromes that are under study for molecular mechanisms involved in the pathogenesis of cancers in general. This presentation describes our investigations of four disorders: the syndrome of sarcomas, breast cancer, and other neoplasms; inheritance of both renal cell carcinoma and a constitutional chromosome translocation in a kindred; familial Wilms' tumor; and the hepatoblastoma-adenomatous polyposis association.