TY - JOUR
T1 - A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11
AU - Australian Breast Cancer Tissue Bank Investigators
AU - Siddiq, Afshan
AU - Couch, Fergus J.
AU - Chen, Gary K.
AU - Lindström, Sara
AU - Eccles, Diana
AU - Millikan, Robert C.
AU - Michailidou, Kyriaki
AU - Stram, Daniel O.
AU - Beckmann, Lars
AU - Rhie, Suhn Kyong
AU - Ambrosone, Christine B.
AU - Aittomäki, Kristiina
AU - Amiano, Pilar
AU - Apicella, Carmel
AU - Baglietto, Laura
AU - Bandera, Elisa V.
AU - Beckmann, Matthias W.
AU - Berg, Christine D.
AU - Bernstein, Leslie
AU - Blomqvist, Carl
AU - Brauch, Hiltrud
AU - Brinton, Louise
AU - Bui, Quang M.
AU - Buring, Julie E.
AU - Buys, Saundra S.
AU - Campa, Daniele
AU - Carpenter, Jane E.
AU - Chasman, Daniel I.
AU - Chang-Claude, Jenny
AU - Chen, Constance
AU - Clavel-Chapelon, Françoise
AU - Cox, Angela
AU - Cross, Simon S.
AU - Czene, Kamila
AU - Deming, Sandra L.
AU - Diasio, Robert B.
AU - Ryan Diver, W.
AU - Dunning, Alison M.
AU - Durcan, Lorraine
AU - Ekici, Arif B.
AU - Fasching, Peter A.
AU - Feigelson, Heather Spencer
AU - Fejerman, Laura
AU - Figueroa, Jonine D.
AU - Fletcher, Olivia
AU - Flesch-Janys, Dieter
AU - Gaudet, Mia M.
AU - Gerty, Susan M.
AU - Rodriguez-Gil, Jorge L.
AU - Severi, Gianluca
PY - 2012/12/15
Y1 - 2012/12/15
N2 - 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 × 10-5in 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.
AB - 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 × 10-5in 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.
UR - http://www.scopus.com/inward/record.url?scp=84984992122&partnerID=8YFLogxK
U2 - 10.1093/hmg/dds381
DO - 10.1093/hmg/dds381
M3 - Article
C2 - 22976474
AN - SCOPUS:84984992122
SN - 0964-6906
VL - 21
SP - 5373
EP - 5384
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 24
ER -