Genome-wide association analysis identifies three new breast cancer susceptibility loci

Ghoussaini M, Fletcher O, Michailidou K, Turnbull C, Schmidt MK, Dicks E, Dennis J, Wang Q, Humphreys MK, Luccarini C, Baynes C, Conroy D, Maranian M, Ahmed S, Driver K, Johnson N, Orr N, Silva IDS, Waisfisz Q, Meijers-Heijboer H, Uitterlinden AG, Rivadeneira F, Hall P, Czene K, Irwanto A, Liu J, Nevanlinna H, Aittomaki K, Blomqvist C, Meindl A, Schmutzler RK, Mueller-Myhsok B, Lichtner P, Chang-Claude J, Hein R, Nickels S, Flesch-Janys D, Tsimiklis H, Makalic E, Schmidt D, Bui M, Hopper JL, Apicella C, Park DJ, Southey M, Hunter DJ, Chanock SJ, Broeks A, Verhoef S, Hogervorst FBL, Fasching P, Lux MP, Beckmann M, Ekici AB, Sawyer E, Tomlinson I, Kerin M, Marme F, Schneeweiss A, Sohn C, Burwinkel B, Guenel P, Truong T, Cordina-Duverger E, Menegaux F, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Milne RL, Rosario Alonso M, Gonzalez-Neira A, Benitez J, Anton-Culver H, Ziogas A, Bernstein L, Dur CC, Brenner H, Mueller H, Arndt V, Stegmaier C, Justenhoven C, Brauch H, Bruening T, Wang-Gohrke S, Eilber U, Doerk T, Schuermann P, Bremer M, Hillemanns P, Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Bermisheva M, Prokofieva D, Khusnutdinova E, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Lambrechts D, Yesilyurt BT, Floris G, Leunen K, Manoukian S, Bonanni B, Fortuzzi S, Peterlongo P, Couch FJ, Wang X, Stevens K, Lee A, Giles GG, Baglietto L, Severi G, Mclean C, Alnaes GG, Kristensen V, Borrensen-Dale AL, John EM, Miron A, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Kauppila S, Andrulis IL, Glendon G, Mulligan AM, Devilee P, Van Asperen CJ, Tollenaar RAEM, Seynaeve C, Figueroa JD, Garcia-Closas M, Brinton L, Lissowska J, Hooning MJ, Hollestelle A, Oldenburg RA, Van Den Ouweland AMW, Cox A, Reed MWR, Shah M, Jakubowska A, Lubinski J, Jaworska K, Durda K, Jones M, Schoemaker M, Ashworth A, Swerdlow A, Beesley J, Chen X, Muir KR, Lophatananon A, Rattanamongkongul S, Chaiwerawattana A, Kang D, Yoo KY, Noh DY, Shen CY, Yu JC, Wu PE, Hsiung CN, Perkins A, Swann R, Velentzis L, Eccles DM, Tapper WJ, Gerty SM, Graham NJ, Ponder BAJ, Chenevix-Trench G, Pharoah PDP, Lathrop M, Dunning AM, Rahman N, Peto J, Easton DF (2012)

Publication Type: Journal article

Publication year: 2012

Journal

Book Volume: 44

Pages Range: 312-8

Journal Issue: 3

DOI: 10.1038/ng.1049

Abstract

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ~8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ~70,000 cases and ~68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

Authors with CRIS profile

Involved external institutions

The Institute of Cancer Research (ICR) United Kingdom (GB) University of Oxford United Kingdom (GB) Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP) France (FR) City of Hope Medical Center United States (USA) (US) Universität Ulm Germany (DE) Dana–Farber Cancer Institute United States (USA) (US) University of Cambridge United Kingdom (GB) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) University of Eastern Finland Finland (FI) Karolinska Institute Sweden (SE) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) Russian Federation (RU) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA) Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) Cancer Prevention Institute of California (CPIC) United States (USA) (US) University of California Irvine United States (USA) (US) Copenhagen University Hospital Denmark (DK) Ruprecht-Karls-Universität Heidelberg Germany (DE) Antoni van Leeuwenhoek Netherlands (NL) National Cancer Institute (NCI) United States (USA) (US) Harvard University United States (USA) (US) The University of Melbourne Australia (AU) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie) Germany (DE) Universität zu Köln Germany (DE) Technische Universität München (TUM) Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) Genome Institute of Singapore Singapore (SG) Erasmus University Medical Center (MC) Netherlands (NL) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) London School of Hygiene and Tropical Medicine United Kingdom (GB) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Centre national de génotypage (CNG) France (FR) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University of Southampton United Kingdom (GB) University of Westminster United Kingdom (GB) Academia Sinica / 中央研究院 Taiwan (TW) Tri-Service General Hospital (TSGH) / 三軍總醫院 Taiwan (TW) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Ministry of Public Health (MOPH) / กระทรวงสาธารณสุข Thailand (TH) Srinakharinwirot University / มหาวิทยาลัยศรีนครินทรวิโรฒ Thailand (TH) University of Warwick United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University of Sheffield United Kingdom (GB) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Leiden University Netherlands (NL) University of Toronto Canada (CA) Cancer Care Ontario Canada (CA) Mount Sinai Hospital (MSH) Canada (CA) Oulun Yliopisto / University of Oulo Finland (FI) The Alfred Hospital Australia (AU) Mayo Clinic United States (USA) (US) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University Hospital Galway Ireland (IE) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Guy's and St Thomas' (NHS Foundation Trust) United Kingdom (GB) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich Germany (DE)

How to cite

APA:

Ghoussaini, M., Fletcher, O., Michailidou, K., Turnbull, C., Schmidt, M.K., Dicks, E.,... Easton, D.F. (2012). Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nature Genetics, 44(3), 312-8. https://dx.doi.org/10.1038/ng.1049

MLA:

Ghoussaini, Maya, et al. "Genome-wide association analysis identifies three new breast cancer susceptibility loci." Nature Genetics 44.3 (2012): 312-8.

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