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Title: Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
Author: Rebbeck, Timothy R.
Friebel, Tara M.
Mitra, Nandita
Wan, Fei
Chen, Stephanie
Andrulis, Irene L.
Apostolou, Paraskevi
Arnold, Norbert
Arun, Banu K.
Barrowdale, Daniel
Benitez, Javier
Niederacher, Dieter
Nussbaum, Robert L.
Offit, Kenneth
Olah, Edith
Olopade, Olufunmilayo I.
Kyung Park, Sue
Piedmonte, Marion
Radice, Paolo
Rappaport-Fuerhauser, Christine
Rookus, Matti A.
Seynaeve, Caroline
Simard, Jacques
Singer, Christian F.
Soucy, Penny
Southey, Melissa
Stoppa-Lyonnet, Dominique
Sukiennicki, Grzegorz
Szabo, Csilla I.
Tancredi, Mariella
KConFab Investigators
Teixeira, Manuel R.
Teo, Soo-Hwang
Terry, Mary Beth
Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)
Thomassen, Mads
Tihomirova, Laima
Epidemiological study of BRCA1 & BRCA2 Mutation Carriers (EMBRACE)
Tischkowitz, Marc
Ewart Toland, Amanda
Toloczko-Grabarek, Aleksandra
Tung, Nadine
Rensburg, Elizabeth J. van
Villano, Danylo
Wang-Gohrke, Shan
Wappenschmidt, Barbara
Weitzel, Jeffrey N.
Zidan, Jamal
Zorn, Kristin K.
Mcguffog, Lesley
Easton, Douglas
Chenevix-Trench, Georgia
Antoniou, Antonis C.
Ramus, Susan J.
Berger, Raanan
Berthet, Pascaline
Borg, Ake
Buys, Saundra S.
Caldes, Trinidad
Carter, Jonathan
Chiquette, Jocelyne
Claes, Kathleen B. M.
Couch, Fergus J.
Cybulski, Cezary
Daly, Mary B.
Hoya, Miguel de la
Díez Gibert, Orland
Domchek, Susan M.
Nathanson, Katherine L.
Durda, Katarzyna
Ellis, Steve
Evans, D. Gareth
Foretova, Lenka
Friedman, Eitan
Frost, Debra
Ganz, Patricia A.
Garber, Judy
Glendon, Gord
Godwin, Andrew K.
Greene, Mark H.
Gronwald, Jacek
Hahnen, Eric
Hallberg, Emily
Hamann, Ute
Hansen, Thomas V. O.
Imyanitov, Evgeny N.
Isaacs, Claudine
Jakubowska, Anna
Janavicius, Ramunas
Jaworska-Bieniek, Katarzyna
John, Esther M.
Karlan, Beth Y.
Kaufman, Bella
Kwong, Ava
Laitman, Yael
Lasset, Christine
Lázaro García, Conxi
Lester, Jenny
Loman, Niklas
Lubinski, Jan
Manoukian, Siranoush
Mitchell, Gillian
Montagna, Marco
Neuhausen, Susan L.
Nevanlinna, Heli
Keywords: Càncer de mama
Breast cancer
Issue Date: 11-Nov-2016
Publisher: BioMed Central
Abstract: Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
Note: Reproducció del document publicat a:
It is part of: Breast Cancer Research, 2016, vol. 18, num. 112
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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