Identification of novel genetic markers of breast cancer survival

Guo Q, Schmidt MK, Kraft P, Canisius S, Chen C, Khan S, Tyrer J, Bolla MK, Wang Q, Dennis J, Michailidou K, Lush M, Kar S, Beesley J, Dunning AM, Shah M, Czene K, Darabi H, Eriksson M, Lambrechts D, Weltens C, Leunen K, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Blomqvist C, Aittomaeki K, Fagerholm R, Muranen TA, Couch FJ, Olson JE, Vachon C, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Broeks A, Hogervorst FB, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Hopper JL, Tsimiklis H, Apicella C, Southey MC, Cox A, Cross SS, Reed MWR, Giles GG, Milne RL, Mclean C, Winqvist R, Pylkaes K, Jukkola-Vuorinen A, Grip M, Hooning MJ, Hollestelle A, Martens JWM, Van Den Ouweland AMW, Marme F, Schneeweiss A, Yang R, Burwinkel B, Figueroa J, Chanock SJ, Lissowska J, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Brenner H, Dieffenbach AK, Arndt V, Holleczek B, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Li J, Brand JS, Humphreys K, Devilee P, Tollenaar RAEM, Seynaeve C, Radice P, Peterlongo P, Bonanni B, Mariani P, Fasching P, Beckmann M, Hein A, Ekici AB, Chenevix-Trench G, Balleine R, Phillips KA, Benitez J, Zamora MP, Perez JIA, Menendez P, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Hamann U, Kabisch M, Ulmer HU, Ruediger T, Margolin S, Kristensen V, Nord S, Evans DG, Abraham JE, Earl HM, Hiller L, Dunn JA, Bowden S, Berg C, Campa D, Diver WR, Gapstur SM, Gaudet MM, Hankinson SE, Hoover RN, Huesing A, Kaaks R, Machiela MJ, Willett W, Barrdahl M, Canzian F, Chin SF, Caldas C, Hunter DJ, Lindstrom S, Garcia-Closas M, Hall P, Easton DF, Eccles DM, Rahman N, Nevanlinna H, Pharoah PDP (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 107

Journal Issue: 5

DOI: 10.1093/jnci/djv081

Abstract

Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival.We conducted a large meta-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided.We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust.This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors.

Authors with CRIS profile

Involved external institutions

Klinikum Mittelbaden Baden-Baden Balg Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) Mayo Clinic United States (USA) (US) University of Toronto Canada (CA) Mount Sinai Hospital (MSH) Canada (CA) Erasmus University Medical Center (MC) Netherlands (NL) University of Hawaii (U.H.) United States (USA) (US) The University of Melbourne Australia (AU) University of Sheffield United Kingdom (GB) The Alfred Hospital Australia (AU) Oulun Yliopisto / University of Oulo Finland (FI) NordLab Finland (FI) Ruprecht-Karls-Universität Heidelberg Germany (DE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University of Sydney (USYD) Australia (AU) Harvard University United States (USA) (US) The Institute of Cancer Research (ICR) United Kingdom (GB) Karolinska Institute Sweden (SE) University of Cambridge United Kingdom (GB) University of Southampton United Kingdom (GB) University of Oxford United Kingdom (GB) University Hospital Galway Ireland (IE) Antoni van Leeuwenhoek Netherlands (NL) Ciber de Enfermedades Raras (CIBERER) Spain (ES) Hospital Universitario La Paz Spain (ES) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Herlev Hospital Denmark (DK) Copenhagen University Hospital Denmark (DK) University of Southern California (USC) United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) King’s College London United Kingdom (GB) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) Leiden University Netherlands (NL) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Hospital Monte Naranco Spain (ES) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Städtisches Klinikum Karlsruhe Germany (DE) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) University of Manchester United Kingdom (GB) University of Warwick United Kingdom (GB) University of Birmingham United Kingdom (GB) American Cancer Society United States (USA) (US)

How to cite

APA:

Guo, Q., Schmidt, M.K., Kraft, P., Canisius, S., Chen, C., Khan, S.,... Pharoah, P.D.P. (2015). Identification of novel genetic markers of breast cancer survival. Journal of the National Cancer Institute, 107(5). https://doi.org/10.1093/jnci/djv081

MLA:

Guo, Qi, et al. "Identification of novel genetic markers of breast cancer survival." Journal of the National Cancer Institute 107.5 (2015).

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