Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22976474
TITLE
A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.
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.
DATE PUBLISHED
2012 Dec 15
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2012/09/13
aheadofprint 2012/10/05
entrez 2012/09/15 06:00
pubmed 2012/09/15 06:00
medline 2013/06/01 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Siddiq A Siddiq Afshan A Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Couch FJ Couch Fergus J FJ
Chen GK Chen Gary K GK
Lindström S Lindström Sara S
Eccles D Eccles Diana D
Millikan RC Millikan Robert C RC
Michailidou K Michailidou Kyriaki K
Stram DO Stram Daniel O DO
Beckmann L Beckmann Lars L
Rhie SK Rhie Suhn Kyong SK
Ambrosone CB Ambrosone Christine B CB
Aittomäki K Aittomäki Kristiina K
Amiano P Amiano Pilar P
Apicella C Apicella Carmel C
Australian Breast Cancer Tissue Bank Investigators
Baglietto L Baglietto Laura L
Bandera EV Bandera Elisa V EV
Beckmann MW Beckmann Matthias W MW
Berg CD Berg Christine D CD
Bernstein L Bernstein Leslie L
Blomqvist C Blomqvist Carl C
Brauch H Brauch Hiltrud H
Brinton L Brinton Louise L
Bui QM Bui Quang M QM
Buring JE Buring Julie E JE
Buys SS Buys Saundra S SS
Campa D Campa Daniele D
Carpenter JE Carpenter Jane E JE
Chasman DI Chasman Daniel I DI
Chang-Claude J Chang-Claude Jenny J
Chen C Chen Constance C
Clavel-Chapelon F Clavel-Chapelon Françoise F
Cox A Cox Angela A
Cross SS Cross Simon S SS
Czene K Czene Kamila K
Deming SL Deming Sandra L SL
Diasio RB Diasio Robert B RB
Diver WR Diver W Ryan WR
Dunning AM Dunning Alison M AM
Durcan L Durcan Lorraine L
Ekici AB Ekici Arif B AB
Fasching PA Fasching Peter A PA
Familial Breast Cancer Study
Feigelson HS Feigelson Heather Spencer HS
Fejerman L Fejerman Laura L
Figueroa JD Figueroa Jonine D JD
Fletcher O Fletcher Olivia O
Flesch-Janys D Flesch-Janys Dieter D
Gaudet MM Gaudet Mia M MM
GENICA Consortium
Gerty SM Gerty Susan M SM
Rodriguez-Gil JL Rodriguez-Gil Jorge L JL
Giles GG Giles Graham G GG
van Gils CH van Gils Carla H CH
Godwin AK Godwin Andrew K AK
Graham N Graham Nikki N
Greco D Greco Dario D
Hall P Hall Per P
Hankinson SE Hankinson Susan E SE
Hartmann A Hartmann Arndt A
Hein R Hein Rebecca R
Heinz J Heinz Judith J
Hoover RN Hoover Robert N RN
Hopper JL Hopper John L JL
Hu JJ Hu Jennifer J JJ
Huntsman S Huntsman Scott S
Ingles SA Ingles Sue A SA
Irwanto A Irwanto Astrid A
Isaacs C Isaacs Claudine C
Jacobs KB Jacobs Kevin B KB
John EM John Esther M EM
Justenhoven C Justenhoven Christina C
Kaaks R Kaaks Rudolf R
Kolonel LN Kolonel Laurence N LN
Coetzee GA Coetzee Gerhard A GA
Lathrop M Lathrop Mark M
Le Marchand L Le Marchand Loic L
Lee AM Lee Adam M AM
Lee IM Lee I-Min IM
Lesnick T Lesnick Timothy T
Lichtner P Lichtner Peter P
Liu J Liu Jianjun J
Lund E Lund Eiliv E
Makalic E Makalic Enes E
Martin NG Martin Nicholas G NG
McLean CA McLean Catriona A CA
Meijers-Heijboer H Meijers-Heijboer Hanne H
Meindl A Meindl Alfons A
Miron P Miron Penelope P
Monroe KR Monroe Kristine R KR
Montgomery GW Montgomery Grant W GW
Müller-Myhsok B Müller-Myhsok Bertram B
Nickels S Nickels Stefan S
Nyante SJ Nyante Sarah J SJ
Olswold C Olswold Curtis C
Overvad K Overvad Kim K
Palli D Palli Domenico D
Park DJ Park Daniel J DJ
Palmer JR Palmer Julie R JR
Pathak H Pathak Harsh H
Peto J Peto Julian J
Pharoah P Pharoah Paul P
Rahman N Rahman Nazneen N
Rivadeneira F Rivadeneira Fernando F
Schmidt DF Schmidt Daniel F DF
Schmutzler RK Schmutzler Rita K RK
Slager S Slager Susan S
Southey MC Southey Melissa C MC
Stevens KN Stevens Kristen N KN
Sinn HP Sinn Hans-Peter HP
Press MF Press Michael F MF
Ross E Ross Eric E
Riboli E Riboli Elio E
Ridker PM Ridker Paul M PM
Schumacher FR Schumacher Fredrick R FR
Severi G Severi Gianluca G
Dos Santos Silva I Dos Santos Silva Isabel I
Stone J Stone Jennifer J
Sund M Sund Malin M
Tapper WJ Tapper William J WJ
Thun MJ Thun Michael J MJ
Travis RC Travis Ruth C RC
Turnbull C Turnbull Clare C
Uitterlinden AG Uitterlinden Andre G AG
Waisfisz Q Waisfisz Quinten Q
Wang X Wang Xianshu X
Wang Z Wang Zhaoming Z
Weaver J Weaver Joellen J
Schulz-Wendtland R Schulz-Wendtland Rüdiger R
Wilkens LR Wilkens Lynne R LR
Van Den Berg D Van Den Berg David D
Zheng W Zheng Wei W
Ziegler RG Ziegler Regina G RG
Ziv E Ziv Elad E
Nevanlinna H Nevanlinna Heli H
Easton DF Easton Douglas F DF
Hunter DJ Hunter David J DJ
Henderson BE Henderson Brian E BE
Chanock SJ Chanock Stephen J SJ
Garcia-Closas M Garcia-Closas Montserrat M
Kraft P Kraft Peter P
Haiman CA Haiman Christopher A CA
Vachon CM Vachon Celine M CM
INVESTIGATORS
JOURNAL
VOLUME: 21
ISSUE: 24
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2012
MONTH: Dec
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2083
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
10118 Cancer Research UK United Kingdom
11692 Cancer Research UK United Kingdom
5U01CA113916 NCI NIH HHS United States
5UO1CA098233 NCI NIH HHS United States
CA 65725 NCI NIH HHS United States
CA-06-503 NCI NIH HHS United States
CA047988 NCI NIH HHS United States
CA109147 NCI NIH HHS United States
CA116201 NCI NIH HHS United States
CA120120 NCI NIH HHS United States
CA122340 NCI NIH HHS United States
CA132839 NCI NIH HHS United States
CA49449 NCI NIH HHS United States
CA50385 NCI NIH HHS United States
CA67262 NCI NIH HHS United States
CA87969 NCI NIH HHS United States
G0700491 Medical Research Council United Kingdom
HL04385 NHLBI NIH HHS United States
HL080467 NHLBI NIH HHS United States
K01 CA160607 NCI NIH HHS United States
K24 CA169004 NCI NIH HHS United States
N01-HD-3-3175 NICHD NIH HHS United States
P30 CA016056-32 NCI NIH HHS United States
P30 CA016086 NCI NIH HHS United States
P30 ES010126 NIEHS NIH HHS United States
P30-ES10126 NIEHS NIH HHS United States
P50 CA058223 NCI NIH HHS United States
P50 CA089393 NCI NIH HHS United States
P50 CA116201 NCI NIH HHS United States
P50-CA58223 NCI NIH HHS United States
R01 CA077398 NCI NIH HHS United States
R01 CA120120 NCI NIH HHS United States
R01 CA122340 NCI NIH HHS United States
R01-CA100374 NCI NIH HHS United States
R01-CA100598 NCI NIH HHS United States
R01-CA63464 NCI NIH HHS United States
R01-CA73629 NCI NIH HHS United States
R01-CA77305 NCI NIH HHS United States
R25 CA092049 NCI NIH HHS United States
R37-CA54281 NCI NIH HHS United States
RFA-CA-06-503 NCI NIH HHS United States
U01 CA69638 NCI NIH HHS United States
U01-CA69417 NCI NIH HHS United States
U01-CA98216 NCI NIH HHS United States
U01-CA98233 NCI NIH HHS United States
U01-CA98710 NCI NIH HHS United States
U01-CA98758 NCI NIH HHS United States
U01CA69631 NCI NIH HHS United States
U19 CA148065 NCI NIH HHS United States
Cancer Research UK United Kingdom
Intramural NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Breast Neoplasms genetics
Female genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Humans genetics
Polymorphism, Single Nucleotide genetics
Receptors, Estrogen genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Receptors, Estrogen
OTHER ID's
OTHERID SOURCE
PMC3510753 NLM