Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women.

Breast cancer research : BCR ·第 18 卷 ·第 1 期 ·0000-00-00

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, 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, de la Hoya Miguel, Diez 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, Investigators KConFab, Kwong Ava, Laitman Yael, Lasset Christine, Lazaro Conxi, Lester Jenny, Loman Niklas, Lubinski Jan, Manoukian Siranoush, Mitchell Gillian, Montagna Marco, Neuhausen Susan L, Nevanlinna Heli, Niederacher Dieter, Nussbaum Robert L, Offit Kenneth, Olah Edith, Olopade Olufunmilayo I, Park Sue Kyung, 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, Teixeira Manuel R, Teo Soo-Hwang, Terry Mary Beth, Thomassen Mads, Tihomirova Laima, Tischkowitz Marc, Toland Amanda Ewart, Toloczko-Grabarek Aleksandra, Tung Nadine, van Rensburg Elizabeth J, 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

摘要

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.,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.,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.,Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.

关键词

BRCA1 BRCA2 Hereditary breast and ovarian cancer Transheterozygosity

文献信息

期刊

Breast cancer research : BCR

期刊简称

Breast Cancer Res

ISSN

1465-5411

发表日期

0000-00-00

收录日期

2016-11-12

更新日期

2016-11-26

语言

英语

国家/地区

England

NLM ID

100927353

外部链接

PubMed 原文查看期刊详情

分析服务

Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women.

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