Clinical impact of molecular genetic diagnosis, genetic counseling, and management of hereditary cancer - Part I: Studies of cancer in families

Hereditary cancer represents approximately 5-10% of the total cancer burden and may account for 60,000 to 120,000 new cancer occurrences this year in the United States. New developments in molecular genetics and the cloning o f cancer-prone genes have intensely fueled interest in dealing with heredit ary forms of cancer. The authors provide an algorithm that depicts the proc ess for the identification, study, and DNA-based genetic counseling of fami lies being investigated under a research proposal at the Hereditary Cancer Institute of Creighton University School of Medicine. They have studied 56 hereditary nonpolyposis colorectal carcinoma families; in 18 of them, assoc iated genomic mutations have been identified in affected members. DNA-based genetic counseling has been provided for seven of these families. The auth ors have also evaluated 131 hereditary breast-ovarian carcinoma families. B RCA1 and BRCA2 mutation searches have been performed for 76 of these famili es; BRCA1 mutations were found in 38 families and BRCA2 mutations in 9. The study of cancer-prone families is a powerful approach to cancer control, p articularly when the germ-line mutation is identified in the family and ind ividuals at high risk can be tested, once they provide informed consent, an d receive DNA-based genetic counseling. Discovery of the germ-line mutation for cancer proneness provides an unparalleled opportunity to predict patie nts' lifetime risk for cancer of specific anatomic sites, inclusive of a pa ttern of multiple primaries. Surveillance and management protocols, when me lded to the particular syndrome's natural history, can be life-saving. Canc er 1999;86:2449-56, (C) 1999 American Cancer Society.