Genetic testing for RAD51C mutations: in the clinic and community. (7th January 2015)

• Record Type: Journal Article
• Authors: Sopik, V.; Akbari, M.R.; Narod, S.A.
• Is Part Of: Clinical genetics. Volume 88:Number 4(2015:Oct.)
• Page Start: 303
• Page End: 312
• Publication Date: 2015-01-07
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12548
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12548-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12548-para-0001">Much of the observed familial clustering of breast and ovarian cancer cannot be explained by mutations in <italic>BRCA1</italic> and <italic>BRCA2</italic>. Several other cancer susceptibility genes have been identified, but their value in routine clinical genetic testing is still unclear. Germline mutations in <italic>RAD51C</italic> have been identified in about 1% of hereditary breast and ovarian cancer families. <italic>RAD51C</italic> mutations are predominantly found in families with a history of ovarian cancer and are rare in families with a history of breast cancer alone. <italic>RAD51C</italic> is primarily an ovarian cancer susceptibility gene. A mutation is present in approximately 1% of unselected ovarian cancers. Among mutation carriers, the lifetime risk of ovarian cancer is approximately 9%. The average age at onset is approximately 60 years; this suggests that preventive oophorectomy can be delayed until after natural menopause. Under current guidelines, genetic testing for <italic>RAD51C</italic> is expected to have a limited impact on ovarian cancer incidence at a population level. This is because the penetrance is 9% to age 80; the great majority of families with mutations would be represented by a single case of ovarian cancer, these are potentially preventable through population screening but not through screening of established ovarian cancer families.</p> </abstract>