A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.

Journal: Human Molecular Genetics
Published:
Abstract

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

Authors
Afshan Siddiq, Fergus Couch, Gary Chen, Sara Lindström, Diana Eccles, Robert Millikan, Kyriaki Michailidou, Daniel Stram, Lars Beckmann, Suhn Rhie, Christine Ambrosone, Kristiina Aittomäki, Pilar Amiano, Carmel Apicella, Elisa Bandera, Matthias Beckmann, Christine Berg, Leslie Bernstein, Carl Blomqvist, Hiltrud Brauch, Louise Brinton, Quang Bui, Julie Buring, Saundra Buys, Daniele Campa, Jane Carpenter, Daniel Chasman, Jenny Chang Claude, Constance Chen, Françoise Clavel Chapelon, Angela Cox, Simon Cross, Kamila Czene, Sandra Deming, Robert Diasio, W Diver, Alison Dunning, Lorraine Durcan, Arif Ekici, Peter Fasching, Heather Feigelson, Jonine Figueroa, Olivia Fletcher, Dieter Flesch Janys, Mia Gaudet, Susan Gerty, Jorge Rodriguez Gil, Carla Van Gils, Andrew Godwin, Nikki Graham, Dario Greco, Per Hall, Susan Hankinson, Arndt Hartmann, Rebecca Hein, Judith Heinz, Robert Hoover, John Hopper, Jennifer Hu, Scott Huntsman, Sue Ingles, Astrid Irwanto, Claudine Isaacs, Kevin Jacobs, Esther John, Christina Justenhoven, Rudolf Kaaks, Laurence Kolonel, Gerhard Coetzee, Mark Lathrop, Loic Le Marchand, Adam Lee, I-min Lee, Timothy Lesnick, Peter Lichtner, Jianjun Liu, Eiliv Lund, Enes Makalic, Nicholas Martin, Catriona Mclean, Hanne Meijers Heijboer, Alfons Meindl, Penelope Miron, Kristine Monroe, Grant Montgomery, Bertram Müller Myhsok, Stefan Nickels, Sarah Nyante, Curtis Olswold, Kim Overvad, Domenico Palli, Daniel Park, Julie Palmer, Harsh Pathak, Julian Peto, Paul Pharoah, Nazneen Rahman, Fernando Rivadeneira, Daniel Schmidt, Rita Schmutzler, Susan Slager, Melissa Southey, Kristen Stevens, Hans-peter Sinn, Michael Press, Eric Ross, Elio Riboli, Paul Ridker, Fredrick Schumacher, Gianluca Severi, Isabel Dos Santos Silva, Jennifer Stone, Malin Sund, William Tapper, Michael Thun, Ruth Travis, Clare Turnbull, Andre Uitterlinden, Quinten Waisfisz, Xianshu Wang, Zhaoming Wang, Joellen Weaver, Rüdiger Schulz Wendtland, Lynne Wilkens, David Van Den Berg, Wei Zheng, Regina Ziegler, Elad Ziv, Heli Nevanlinna, Douglas Easton, David Hunter, Brian Henderson, Stephen Chanock, Montserrat Garcia Closas, Peter Kraft, Christopher Haiman, Celine Vachon
Relevant Conditions

Breast Cancer