9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium

H Warren, F Dudbridge, O Fletcher, N Orr, N Johnson, JL Hopper, C Apicella, MC Southey, M Mahmoodi, Marjanka K Schmidt, A Broeks, S Cornelissen, LM Braaf, KR Muir, A Lophatananon, A Chaiwerawattana, S Wiangnon, PA Fasching, MW Beckmann, AB EkiciR Schulz-Wendtland, EJ Sawyer, I Tomlinson, M Kerin, B Burwinkel, F Marme, A Schneeweiss, C Sohn, P Guenel, P Laurent-Puig, C Mulot, SE Bojesen, SF Nielsen, H Flyger, BG Nordestgaard, RL Milne, J Benitez, JI Arias-Perez, MP Zamora, H Anton-Culver, A Ziogas, L Bernstein, CC Dur, H Brenner, H Muller, V Arndt, A Langheinz, A Meindl, M Golatta, CR Bartram, RK Schmutzler, H Brauch, C Justenhoven, T Bruning, J Chang-Claude, S Wang-Gohrke, U Eilber, T Dork, P Schurmann, M Bremer, P Hillemanns, H Nevanlinna, TA Muranen, K Aittomaki, C Blomqvist, N Bogdanova, N Antonenkova, Y Rogov, M Bermisheva, D Prokofyeva, G Zinnatullina, E Khusnutdinova, A Lindblom, S Margolin, A Mannermaa, VM Kosma, JM Hartikainen, V Kataja, G Chenevix-Trench, J Beesley, XQ Chen, D Lambrechts, A Smeets, R Paridaens, C Weltens, D Flesch-Janys, K Buck, S Behrens, P Peterlongo, L Bernard, S Manoukian, P Radice, FJ Couch, C Vachon, XS Wang, J Olson, G Giles, L Baglietto, CA McLean, G Severi, EM John, A Miron, R Winqvist, K Pylkas, A Jukkola-Vuorinen, M Grip, IL Andrulis, JA Knight, AM Mulligan, N Weerasooriya, P Devilee, RAEM Tollenaar, John Martens, Caroline Seynaeve, Maartje Hooning, Antoinette Hollestelle, Agnes Jager, Madeleine Tilanus - Linthorst, P Hall, K Czene, JJ Liu, JM Li, A Cox, SS Cross, IW Brock, MWR Reed, P Pharoah, FM Blows, AM Dunning, M Ghous-saini, A Ashworth, A Swerdlow, M Jones, M Schoemaker, DF Easton, M Humphreys, Q (Qing) Wang, J Peto, I dos-Santos-Silva, T Truong

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Abstract

Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 x 10(-29)] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (P-het) -1.3 x 10(-143)], but n Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype. Cancer Epidemiol Biomarkers Prev; 21(10); 1783-91. (c) 2012 AACR.
Original languageUndefined/Unknown
Pages (from-to)1783-1791
Number of pages9
JournalCancer Epidemiology Biomarkers & Prevention
Volume21
Issue number10
DOIs
Publication statusPublished - 2012

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