19p13.1 is a triple-negative-specific breast cancer susceptibility locus.
;
Nichola
Johnson
;
Olivia
Fletcher
;
Isabel
Dos Santos Silva
;
Peter A
Fasching
;
Matthias W
Beckmann
;
Arndt
Hartmann
;
Arif B
Ekici
;
Artitaya
Lophatananon
;
Kenneth
Muir
;
Puttisak
Puttawibul
;
Surapon
Wiangnon
;
Marjanka K
Schmidt
;
Annegien
Broeks
;
Linde M
Braaf
;
Efraim H
Rosenberg
;
John L
Hopper
;
Carmel
Apicella
;
Daniel J
Park
;
Melissa C
Southey
;
Anthony J
Swerdlow
;
Alan
Ashworth
;
Nicholas
Orr
;
Minouk J
Schoemaker
;
Hoda
Anton-Culver
;
Argyrios
Ziogas
;
Leslie
Bernstein
;
Christina Clarke
Dur
;
Chen-Yang
Shen
;
Jyh-Cherng
Yu
;
Huan-Ming
Hsu
;
Chia-Ni
Hsiung
;
Ute
Hamann
;
Thomas
Dünnebier
;
Thomas
Rüdiger
;
Hans Ulrich
Ulmer
;
Paul P
Pharoah
;
Alison M
Dunning
;
Manjeet K
Humphreys
;
Qin
Wang
;
Angela
Cox
;
Simon S
Cross
;
Malcom W
Reed
;
Per
Hall
;
Kamila
Czene
;
Christine B
Ambrosone
;
Foluso
Ademuyiwa
;
Helena
Hwang
;
Diana M
Eccles
;
Montserrat
Garcia-Closas
;
Jonine D
Figueroa
;
Mark E
Sherman
;
Jolanta
Lissowska
;
Peter
Devilee
;
Caroline
Seynaeve
;
Rob AEM
Tollenaar
;
Maartje J
Hooning
;
Irene L
Andrulis
;
Julia A
Knight
;
Gord
Glendon
;
Anna Marie
Mulligan
;
Robert
Winqvist
;
Katri
Pylkäs
;
Arja
Jukkola-Vuorinen
;
Mervi
Grip
;
Esther M
John
;
Alexander
Miron
;
Grethe Grenaker
Alnæs
;
Vessela
Kristensen
;
Anne-Lise
Børresen-Dale
;
Graham G
Giles
;
Laura
Baglietto
;
Catriona A
McLean
;
Gianluca
Severi
;
Matthew L
Kosel
;
VS
Pankratz
;
Susan
Slager
;
Janet E
Olson
;
Paolo
Radice
;
Paolo
Peterlongo
;
Siranoush
Manoukian
;
Monica
Barile
;
Diether
Lambrechts
;
Sigrid
Hatse
;
Anne-Sophie
Dieudonne
;
Marie-Rose
Christiaens
;
Georgia
Chenevix-Trench
;
kConFab Investigators
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AOCS Group
;
Jonathan
Beesley
;
Xiaoqing
Chen
;
Arto
Mannermaa
;
Veli-Matti
Kosma
;
Jaana M
Hartikainen
;
Ylermi
Soini
;
Douglas F
Easton
;
Fergus J
Couch
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(2012)
19p13.1 is a triple-negative-specific breast cancer susceptibility locus.
Cancer research, 72 (7).
pp. 1795-1803.
ISSN 0008-5472
DOI: 10.1158/0008-5472.CAN-11-3364
The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 × 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 × 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 × 10(-13)]. Thus, 19p13.1 is the first triple-negative-specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways.