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

Carcinogenesis ·第 35 卷 ·第 5 期 ·2014-06-24

Purrington Kristen S, Slager Susan, Eccles Diana, Yannoukakos Drakoulis, Fasching Peter A, Miron Penelope, Carpenter Jane, Chang-Claude Jenny, Martin Nicholas G, Montgomery Grant W, Kristensen Vessela, Anton-Culver Hoda, Goodfellow Paul, Tapper William J, Rafiq Sajjad, Gerty Susan M, Durcan Lorraine, Konstantopoulou Irene, Fostira Florentia, Vratimos Athanassios, Apostolou Paraskevi, Konstanta Irene, Kotoula Vassiliki, Lakis Sotiris, Dimopoulos Meletios A, Skarlos Dimosthenis, Pectasides Dimitrios, Fountzilas George, Beckmann Matthias W, Hein Alexander, Ruebner Matthias, Ekici Arif B, Hartmann Arndt, Schulz-Wendtland Ruediger, Renner Stefan P, Janni Wolfgang, Rack Brigitte, Scholz Christoph, Neugebauer Julia, Andergassen Ulrich, Lux Michael P, Haeberle Lothar, Clarke Christine, Pathmanathan Nirmala, Rudolph Anja, Flesch-Janys Dieter, Nickels Stefan, Olson Janet E, Ingle James N, Olswold Curtis, Slettedahl Seth, Eckel-Passow Jeanette E, Anderson S Keith, Visscher Daniel W, Cafourek Victoria L, Sicotte Hugues, Prodduturi Naresh, Weiderpass Elisabete, Bernstein Leslie, Ziogas Argyrios, Ivanovich Jennifer, Giles Graham G, Baglietto Laura, Southey Melissa, Kosma Veli-Matti, Fischer Hans-Peter, , Reed Malcom W R, Cross Simon S, Deming-Halverson Sandra, Shrubsole Martha, Cai Qiuyin, Shu Xiao-Ou, Daly Mary, Weaver Joellen, Ross Eric, Klemp Jennifer, Sharma Priyanka, Torres Diana, Rüdiger Thomas, Wölfing Heidrun, Ulmer Hans-Ulrich, Försti Asta, Khoury Thaer, Kumar Shicha, Pilarski Robert, Shapiro Charles L, Greco Dario, Heikkilä Päivi, Aittomäki Kristiina, Blomqvist Carl, Irwanto Astrid, Liu Jianjun, Pankratz Vernon Shane, Wang Xianshu, Severi Gianluca, Mannermaa Arto, Easton Douglas, Hall Per, Brauch Hiltrud, Cox Angela, Zheng Wei, Godwin Andrew K, Hamann Ute, Ambrosone Christine, Toland Amanda Ewart, Nevanlinna Heli, Vachon Celine M, Couch Fergus J

摘要

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.

文献信息

期刊

Carcinogenesis

期刊简称

Carcinogenesis

ISSN

0143-3334

发表日期

2014-06-24

收录日期

2014-04-30

更新日期

2016-10-19

语言

英语

国家/地区

England

NLM ID

8008055

外部链接

PubMed 原文查看期刊详情

分析服务

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

联系地址

微信公众号