GENETIC TRANSMISSION OF SUSCEPTIBILITY TO CANCER IN FAMILIES OF CHILDREN WITH SOFT-TISSUE SARCOMAS

BACKGROUND. This article presents analysis of clinical and family data for 239 patients with childhood soft tissue sarcoma (STS) treated at the Institut Gustave Roussy in Villejuif. METHODS. A molecular study w as performed to detect germline p53 mutations in the 44 families in wh ich at least 1 relative developed cancer before the age of 46 or in wh ich the proband had a second neoplasm. Mutations were found in five fa milies. Standardized incidence ratio calculation and segregation analy sis were used to study cancer occurrence in 4448 relatives, including first- and second-degree relatives and first cousins. RESULTS. An exce ss of brain tumors was observed in all relatives, and of breast carcin oma and STS in first-degree relatives of patients with STS. An excess of breast carcinoma was observed only in young mothers of patients wit h rhabdomyosarcoma. This excess might be mostly linked to the presence of a germline p53 mutation because it was no more significant when ex cluding families in which such a mutation existed. No association betw een breast carcinoma in the mother and rhabdomyosarcoma of the genitou rinary tract in the proband was observed. This should be kept in mind when developing a screening strategy for breast carcinoma in mothers o f patients with STS. Segregation analysis showed evidence for transmis sion of an autosomal dominant gene with complete penetrance by the age of 84. The genetic component was explained primarily by p53 germline mutations. CONCLUSIONS. These results show that most relatives of pati ents with STS are at the same risk for cancer as the general populatio n. (C) 1996 American Cancer Society.