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 of cancer-prone genes have intensely fueled interest in dealing with hereditary forms of cancer. The authors provide an algorithm that depicts the process for the identification, study, and DNA-based genetic counseling of families 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, associated genomic mutations have been identified in affected members. DNA-based genetic counseling has been provided for seven of these families. The authors have also evaluated 131 hereditary breast-ovarian carcinoma families. BRCA1 and BRCA2 mutation searches have been performed for 76 of these families; 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, particularly when the germ-line mutation is identified in the family and individuals at high risk can be tested, once they provide informed consent, and receive DNA-based genetic counseling. Discovery of the germ-line mutation for cancer proneness provides an unparalleled opportunity to predict patients' life-time risk for cancer of specific anatomic sites, inclusive of a pattern of multiple primaries. Surveillance and management protocols, when melded to the particular syndrome's natural history, can be life-saving.
Lynch
H T
HT
Department of Preventive Medicine, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Watson
P
P
Shaw
T G
TG
Lynch
J F
JF
Harty
A E
AE
Franklin
B A
BA
Kapler
C R
CR
Tinley
S T
ST
Liu
B
B
D002985:Clinical Protocols; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005817:Genetic Counseling; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008318:Malpractice; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010819:Physician's Role
D004273:DNA, Neoplasm