Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

Purrington KS, Slager S, Eccles D, Yannoukakos D, Fasching PA, Miron P, Carpenter J, Chang-Claude J, Martin NG, Montgomery GW, Kristensen V, Anton-Culver H, Goodfellow P, Tapper WJ, Rafiq S, Gerty SM, Durcan L, Konstantopoulou I, Fostira F, Vratimos A, Apostolou P, Konstanta I, Kotoula V, Lakis S, Dimopoulos MA, Skarlos D, Pectasides D, Fountzilas G, Beckmann M, Hein A, Ruebner M, Ekici AB, Hartmann A, Schulz-Wendtland R, Renner S, Janni W, Rack B, Scholz C, Neugebauer J, Andergassen U, Lux MP, Häberle L, Clarke C, Pathmanathan N, Rudolph A, Flesch-Janys D, Nickels S, Olson JE, Ingle JN, Olswold C, Slettedahl S, Eckel-Passow JE, Anderson SK, Visscher DW, Cafourek VL, Sicotte H, Prodduturi N, Weiderpass E, Bernstein L, Ziogas A, Ivanovich J, Giles GG, Baglietto L, Southey M, Kosma VM, Fischer HP, Reed MWR, Cross SS, Deming-Halverson S, Shrubsole M, Cai Q, Shu XO, Daly M, Weaver J, Ross E, Klemp J, Sharma P, Torres D, Rudiger T, Wolfing H, Ulmer HU, Forsti A, Khoury T, Kumar S, Pilarski R, Shapiro CL, Greco D, Heikkila P, Aittomaki K, Blomqvist C, Irwanto A, Liu J, Pankratz VS, Wang X, Severi G, Mannermaa A, Easton D, Hall P, Brauch H, Cox A, Zheng W, Godwin AK, Hamann U, Ambrosone C, Toland AE, Nevanlinna H, Vachon CM, Couch FJ (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option B

Book Volume: 35

Pages Range: 1012-9

Journal Issue: 5

DOI: 10.1093/carcin/bgt404

Abstract

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.

Authors with CRIS profile

Involved external institutions

Mayo Clinic United States (USA) (US) University of Southampton United Kingdom (GB) National Centre for Scientific Research (NCSR) "Demokritos" Greece (GR) University of California Los Angeles (UCLA) United States (USA) (US) Dana–Farber Cancer Institute United States (USA) (US) Aristotle University of Thessaloniki Greece (GR) National and Kapodistrian University of Athens Greece (GR) Universitätsklinikum Ulm Germany (DE) Ludwig-Maximilians-Universität (LMU) Germany (DE) University of Sydney (USYD) Australia (AU) Westmead Hospital Australia (AU) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Universitetet i Tromsø / The Arctic University of Norway (UiT) Norway (NO) City of Hope Medical Center United States (USA) (US) Washington University United States (USA) (US) University of California Irvine United States (USA) (US) Cancer Council Victoria Australia (AU) University of Sheffield United Kingdom (GB) The University of Melbourne Australia (AU) University of Eastern Finland Finland (FI) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Vanderbilt University United States (USA) (US) Fox Chase Cancer Center United States (USA) (US) University of Pennsylvania United States (USA) (US) University of Kansas (KU) United States (USA) (US) Städtisches Klinikum Karlsruhe Germany (DE) Klinikum Mittelbaden Baden-Baden Balg Germany (DE) Lund University / Lunds universitet Sweden (SE) Roswell Park Cancer Institute United States (USA) (US) Ohio State University United States (USA) (US) Helsingin yliopisto / University of Helsinki Finland (FI) Genome Institute of Singapore Singapore (SG) University of Cambridge United Kingdom (GB) Karolinska Institute Sweden (SE) Robert-Bosch-Krankenhaus Germany (DE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO)

How to cite

APA:

Purrington, K.S., Slager, S., Eccles, D., Yannoukakos, D., Fasching, P.A., Miron, P.,... Couch, F.J. (2014). Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. Carcinogenesis, 35(5), 1012-9. https://dx.doi.org/10.1093/carcin/bgt404

MLA:

Purrington, Kristen S., et al. "Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer." Carcinogenesis 35.5 (2014): 1012-9.

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