19p13.1 is a triple-negative-specific breast cancer susceptibility locus.

Cancer research ·Vol. 72 ·No. 7 ·2012-05-24

Stevens Kristen N, Fredericksen Zachary, Vachon Celine M, Wang Xianshu, Margolin Sara, Lindblom Annika, Nevanlinna Heli, Greco Dario, Aittomäki Kristiina, Blomqvist Carl, Chang-Claude Jenny, Vrieling Alina, Flesch-Janys Dieter, Sinn Hans-Peter, Wang-Gohrke Shan, Nickels Stefan, Brauch Hiltrud, , Ko Yon-Dschun, Fischer Hans-Peter, Schmutzler Rita K, Meindl Alfons, Bartram Claus R, Schott Sarah, Engel Christoph, Godwin Andrew K, Weaver Joellen, Pathak Harsh B, Sharma Priyanka, Brenner Hermann, Müller Heiko, Arndt Volker, Stegmaier Christa, Miron Penelope, Yannoukakos Drakoulis, Stavropoulou Alexandra, Fountzilas George, Gogas Helen J, Swann Ruth, Dwek Miriam, Perkins Annie, Milne Roger L, Benítez Javier, Zamora María Pilar, Pérez José Ignacio Arias, Bojesen Stig E, Nielsen Sune F, Nordestgaard Børge G, Flyger Henrik, Guénel Pascal, Truong Thérèse, Menegaux Florence, Cordina-Duverger Emilie, Burwinkel Barbara, Marmé Frederick, Schneeweiss Andreas, Sohn Christof, Sawyer Elinor, Tomlinson Ian, Kerin Michael J, Peto Julian, Johnson Nichola, Fletcher Olivia, Dos Santos Silva Isabel, Fasching Peter A, Beckmann Matthias W, Hartmann Arndt, Ekici Arif B, Lophatananon Artitaya, Muir Kenneth, Puttawibul Puttisak, Wiangnon Surapon, Schmidt Marjanka K, Broeks Annegien, Braaf Linde M, Rosenberg Efraim H, Hopper John L, Apicella Carmel, Park Daniel J, Southey Melissa C, Swerdlow Anthony J, Ashworth Alan, Orr Nicholas, Schoemaker Minouk J, Anton-Culver Hoda, Ziogas Argyrios, Bernstein Leslie, Dur Christina Clarke, Shen Chen-Yang, Yu Jyh-Cherng, Hsu Huan-Ming, Hsiung Chia-Ni, Hamann Ute, Dünnebier Thomas, Rüdiger Thomas, Ulmer Hans Ulrich, Pharoah Paul P, Dunning Alison M, Humphreys Manjeet K, Wang Qin, Cox Angela, Cross Simon S, Reed Malcom W, Hall Per, Czene Kamila, Ambrosone Christine B, Ademuyiwa Foluso, Hwang Helena, Eccles Diana M, Garcia-Closas Montserrat, Figueroa Jonine D, Sherman Mark E, Lissowska Jolanta, Devilee Peter, Seynaeve Caroline, Tollenaar Rob A E M, Hooning Maartje J, Andrulis Irene L, Knight Julia A, Glendon Gord, Mulligan Anna Marie, Winqvist Robert, Pylkäs Katri, Jukkola-Vuorinen Arja, Grip Mervi, John Esther M, Miron Alexander, Alnæs Grethe Grenaker, Kristensen Vessela, Børresen-Dale Anne-Lise, Giles Graham G, Baglietto Laura, McLean Catriona A, Severi Gianluca, Kosel Matthew L, Pankratz V S, Slager Susan, Olson Janet E, Radice Paolo, Peterlongo Paolo, Manoukian Siranoush, Barile Monica, Lambrechts Diether, Hatse Sigrid, Dieudonne Anne-Sophie, Christiaens Marie-Rose, Chenevix-Trench Georgia, , , Beesley Jonathan, Chen Xiaoqing, Mannermaa Arto, Kosma Veli-Matti, Hartikainen Jaana M, Soini Ylermi, Easton Douglas F, Couch Fergus J

Abstract

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.

Article Info

Journal

Cancer research

Abbr.

Cancer Res

ISSN

0008-5472

Published

2012-05-24

Indexed

2012-04-04

Updated

2016-11-22

Language

English

Country/Region

United States

NLM ID

2984705R

External Links

PubMed source View journal details

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19p13.1 is a triple-negative-specific breast cancer susceptibility locus.

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