A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer.

Christopher A Haiman; Gary K Chen; Celine M Vachon; Federico Canzian; Alison Dunning; Robert C Millikan; Xianshu Wang; Foluso Ademuyiwa; Shahana Ahmed; Christine B Ambrosone; +121 more... Laura Baglietto; Rosemary Balleine; Elisa V Bandera; Matthias W Beckmann; Christine D Berg; Leslie Bernstein; Carl Blomqvist; William J Blot; Hiltrud Brauch; Julie E Buring; Lisa A Carey; Jane E Carpenter; Jenny Chang-Claude; Stephen J Chanock; Daniel I Chasman; Christine L Clarke; Angela Cox; Simon S Cross; Sandra L Deming; Robert B Diasio; Athanasios M Dimopoulos; W Ryan Driver; Thomas Dünnebier; Lorraine Durcan; Diana Eccles; Christopher K Edlund; Arif B Ekici; Peter A Fasching; Heather S Feigelson; Dieter Flesch-Janys; Florentia Fostira; Asta Försti; George Fountzilas; Susan M Gerty; Gene Environment Interaction and Breast Cancer in Germany (GENIC; Graham G Giles; Andrew K Godwin; Paul Goodfellow; Nikki Graham; Dario Greco; Ute Hamann; Susan E Hankinson; Arndt Hartmann; Rebecca Hein; Judith Heinz; Andrea Holbrook; Robert N Hoover; Jennifer J Hu; David J Hunter; Sue A Ingles; Astrid Irwanto; Jennifer Ivanovich; Esther M John; Nicola Johnson; Arja Jukkola-Vuorinen; Rudolf Kaaks; Yon-Dschun Ko; Laurence N Kolonel; Irene Konstantopoulou; Veli-Matti Kosma; Swati Kulkarni; Diether Lambrechts; Adam M Lee; Loïc Le Marchand; Timothy Lesnick; Jianjun Liu; Sara Lindstrom; Arto Mannermaa; Sara Margolin; Nicholas G Martin; Penelope Miron; Grant W Montgomery; Heli Nevanlinna; Stephan Nickels; Sarah Nyante; Curtis Olswold; Julie Palmer; Harsh Pathak; Dimitrios Pectasides; Charles M Perou; Julian Peto

; Paul DP Pharoah; Loreall C Pooler; Michael F Press; Katri Pylkäs; Timothy R Rebbeck; Jorge L Rodriguez-Gil; Lynn Rosenberg; Eric Ross; Thomas Rüdiger; Isabel dos Santos Silva; Elinor Sawyer; Marjanka K Schmidt; Rüdiger Schulz-Wendtland; Fredrick Schumacher; Gianluca Severi; Xin Sheng; Lisa B Signorello; Hans-Peter Sinn; Kristen N Stevens; Melissa C Southey; William J Tapper; Ian Tomlinson; Frans BL Hogervorst; Els Wauters; JoEllen Weaver; Hans Wildiers; Robert Winqvist; David Van Den Berg; Peggy Wan; Lucy Y Xia; Drakoulis Yannoukakos; Wei Zheng; Regina G Ziegler; Afshan Siddiq; Susan L Slager; Daniel O Stram; Douglas Easton; Peter Kraft; Brian E Henderson; Fergus J Couch; (2011) A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nature genetics, 43 (12). pp. 1210-1214. ISSN 1061-4036 DOI: 10.1038/ng.985

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Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.