To identify genetic determinants of human cancer, cancer families and genetic disorders predisposing to neoplasia are studied in an interdisciplinary approach to gain insights into human carcinogenesis. Study of 47 patients from 11 families with neurofibromatosis 2 confirmed that posterior subcapsular lens opacities (cataracts) are a frequent and early feature of the disorder whose major manifestation is bilateral acoustic neuromas that lead to deafness and loss of balance. Cytogenetic evaluation of 20 affected members of five families with the nevoid basal cell carcinoma syndrome rejected prior suggestions that elevated levels of sister chromatid exchanges and chromosomal fragility are a feature of the syndrome. Since a positive family history is a major determinant of breast cancer, we developed a method that could be used in counseling to estimate the chance that a woman with a given age and set of risk factors will get breast cancer in a specific interval of time; if women understand an accurate estimate of their own risk, they may be motivated to participate in effective surveillance or even prophylactic mastectomy. Fourteen review articles and eight lectures were prepared to disseminate these and prior findings. Genetics consultations resulted in a segregation analysis of acute appendicitis in the young and in a survey of medical geneticists' choices when faced with ethical dilemmas in clinical practice.
