Prevalence and penetrance of BRCA1 and BRCA2 germline mutations in Colombian breast cancer patients

• Verfasst von: Tórres, Maria [VerfasserIn]
• Verfasst von: Lorenzo Bermejo, Justo [VerfasserIn]
• Verfasst von: Hamann, Ute [VerfasserIn]
• Titel: Prevalence and penetrance of BRCA1 and BRCA2 germline mutations in Colombian breast cancer patients
• Verf.angabe: D. Torres, J. Lorenzo Bermejo, M.U. Rashid, I. Briceño, F. Gil, A. Beltran, V. Ariza & U. Hamann
• E-Jahr: 2017
• Jahr: 05 July 2017
• Umfang: 9 S.
• Fussnoten: Published online: 05 July 2017 ; Gesehen am 18.07.2018
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2017
• Band/Heft Quelle: 7(2017) Artikel-Nummer 4713, 9 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-017-05056-y
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1577729374

Abstract

Pathogenic BRCA1/2 germline mutations confer high risks of breast and ovarian cancer to women of European ancestry. Characterization of BRCA1/2 mutations in other ethnic groups is also medically important. We comprehensively screened 68 Colombian breast/ovarian cancer families for small-range mutations, 221 families for large-genomic rearrangements, and 1,022 unselected breast cancer cases for Colombian founder mutations in BRCA1/2. The risk of cancer among relatives of mutation carriers and the mutation penetrance were estimated by survival analysis. Identified BRCA2 mutations included 6310delGA and the recurrent 1991del4 mutations. A novel large BRCA2 deletion was found in 0.9% of the screened families. Among unselected breast cancer cases, 3.3% tested positive for BRCA1/3450del4, 2.2% for BRCA1/A1708E, 1.1% for BRCA2/3034del4, and 0.4% for BRCA2/1991del4. Female relatives of carriers of BRCA1/2 founder mutations showed a 5.90 times higher risk of breast cancer, when the woman herself carried a BRCA1 mutation compared to a non-carrier (95% CI 2.01-17.3). The estimated cumulative risk of breast cancer by age 70 years for BRCA1 mutations carriers was 14% (95% CI 5-38) compared to 3% for the general Colombian population (relative risk of breast cancer 4.05). Together with known founder mutations, reported novel variants may ease a cost-effective BRCA1/2 screening in women with Colombian ancestry.