A cancer family syndrome in twenty-four kindreds.

TLDR

The syndrome’s diverse tumor spectrum indicates distinct pathogenetic mechanisms from single‑organ hereditary cancers. Diagnosis is currently clinical, but laboratory markers are needed to identify high‑risk families and uncover shared susceptibility mechanisms. In 24 kindreds, 151 relatives were affected in an autosomal dominant pattern, with 79 % diagnosed before age 45, including 50 sarcomas, 28 breast cancers, and excess brain, leukemia, and adrenal tumors, accounting for 73 % of multiple primaries and 6 radiotherapy‑related second cancers.

Abstract

A search of the Cancer Family Registry of the National Cancer Institute revealed 24 kindreds with the syndrome of sarcoma, breast carcinoma, and other neoplasms in young patients. Cancer developed in an autosomal dominant pattern in 151 blood relatives, 119 (79%) of whom were affected before 45 years of age. These young patients had a total of 50 bone and soft tissue sarcomas of diverse histological subtypes and 28 breast cancers. Additional features of the syndrome included an excess of brain tumors (14 cases), leukemia (9 cases), and adrenocortical carcinoma (4 cases) before age 45 years. These neoplasms also accounted for 73% of the multiple primary cancers occurring in 15 family members. Six of these patients had second cancers linked to radiotherapy. The diversity of tumor types in this syndrome suggests pathogenetic mechanisms which differ from hereditary cancers arising in single organs or tissues. The syndrome is presently diagnosed on clinical grounds; laboratory markers are needed to identify high-risk individuals and families and to provide insights into susceptibility mechanisms that may be shared by a wide variety of cancers.