DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Breast cancer (estrogen-receptor negative, progesterone-receptor negative, and human epidermal growth factor-receptor negative). The EFO term triple-negative breast cancer was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: triple-negative breast cancer

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

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

TITLE:

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

JOURNAL:

Carcinogenesis May 2014, Vol 35, pp. 1012-9

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. PUBMED: 24325915
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