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

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title = "Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer",
abstract = "In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.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 x 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 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 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 x 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.",
author = "Purrington, {Kristen S.} and Susan Slager and Diana Eccles and Drakoulis Yannoukakos and Fasching, {Peter A.} and Penelope Miron and Jane Carpenter and Jenny Chang-Claude and Martin, {Nicholas G.} and Montgomery, {Grant W.} and Vessela Kristensen and Hoda Anton-Culver and Paul Goodfellow and Tapper, {William J.} and Sajjad Rafiq and Gerty, {Susan M.} and Lorraine Durcan and Irene Konstantopoulou and Florentia Fostira and Athanassios Vratimos and Paraskevi Apostolou and Irene Konstanta and Vassiliki Kotoula and Sotiris Lakis and Dimopoulos, {Meletios A.} and Dimosthenis Skarlos and Dimitrios Pectasides and George Fountzilas and Beckmann, {Matthias W.} and Alexander Hein and Matthias Ruebner and Ekici, {Arif B.} and Arndt Hartmann and Ruediger Schulz-Wendtland and Renner, {Stefan P.} and Wolfgang Janni and Brigitte Rack and Christoph Scholz and Julia Neugebauer and Ulrich Andergassen and Lux, {Michael P.} and Lothar Haeberle and Christine Clarke and Nirmala Pathmanathan and Anja Rudolph and Dieter Flesch-Janys and Stefan Nickels and Olson, {Janet E.} and Ingle, {James N.} and Curtis Olswold and Seth Slettedahl and Eckel-Passow, {Jeanette E.} and Anderson, {S. Keith} and Visscher, {Daniel W.} and Cafourek, {Victoria L.} and Hugues Sicotte and Naresh Prodduturi and Elisabete Weiderpass and Leslie Bernstein and Argyrios Ziogas and Jennifer Ivanovich and Giles, {Graham G.} and Laura Baglietto and Melissa Southey and Veli-Matti Kosma and Hans-Peter Fischer and Reed, {Malcom W. R.} and Cross, {Simon S.} and Sandra Deming-Halverson and Martha Shrubsole and Qiuyin Cai and Xiao-Ou Shu and Mary Daly and JoEllen Weaver and Eric Ross and Jennifer Klemp and Priyanka Sharma and Diana Torres and Thomas Rudiger and Heidrun Wolfing and Hans-Ulrich Ulmer and Asta F{\"o}rsti and Thaer Khoury and Shicha Kumar and Robert Pilarski and Shapiro, {Charles L.} and Dario Greco and Paivi Heikkila and Kristiina Aittomaki and Carl Blomqvist and Astrid Irwanto and Jianjun Liu and Pankratz, {Vernon Shane} and Xianshu Wang and Gianluca Severi and Arto Mannermaa and Douglas Easton and Per Hall and Hiltrud Brauch and Angela Cox and Wei Zheng and Godwin, {Andrew K.} and Ute Hamann and Christine Ambrosone and Toland, {Amanda Ewart} and Heli Nevanlinna and Vachon, {Celine M.} and Couch, {Fergus J.}",
year = "2014",
doi = "10.1093/carcin/bgt404",
language = "English",
volume = "35",
pages = "1012--1019",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "5",