Study of preneoplastic genetic diseases with a high risk of cancer may help detect environmental and genetic influences in carcinogenesis, especially when appropriate laboratory assays are used. Neurofibromatosis, an autosomal dominant disorder with a predisposition to cancer, received emphasis. Results on 12 families show linkage to the gene for the receptor for nerve growth factor, with a lod score of 4.4 at a recombination distance of 14 centimorgans. Forty-year follow-up of 212 neurofibromatosis patients in Denmark permitted life-table analysis: survival was worst for females who were the original probands, slightly better in male probands, and only slightly less than rates expected in the general population in affected relatives. The relative risk for malignant neoplasms was 4.0 in probands, but only marginally elevated in relatives. Similar multidisciplinary approaches to three other preneoplastic syndromes revealed, in the nevoid basal cell carcinoma syndrome, a lod score of 1.2 to amylase 1 on chromosome 1p, and an association with auditory defects; in the dysplastic nevus syndrome, a possible excess of chromosome breaks; on multiple endocrine neoplasia, type 1, no firm linkage to 28 polymorphic protein loci.
