9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium.

Helen Warren ; Frank Dudbridge ORCID logo ; Olivia Fletcher ; Nick Orr ; Nichola Johnson ; John L Hopper ; Carmel Apicella ; Melissa C Southey ; Maryam Mahmoodi ; Marjanka K Schmidt ; +133 more... Annegien Broeks ; Sten Cornelissen ; Linda M Braaf ; Kenneth R Muir ; Artitaya Lophatananon ; Arkom Chaiwerawattana ; Surapon Wiangnon ; Peter A Fasching ; Matthias W Beckmann ; Arif B Ekici ; Ruediger Schulz-Wendtland ; Elinor J Sawyer ; Ian Tomlinson ; Michael Kerin ; Barbara Burwinkel ; Frederik Marme ; Andreas Schneeweiss ; Christof Sohn ; Pascal Guénel ; Thérèse Truong ; Pierre Laurent-Puig ; Claire Mulot ; Stig E Bojesen ; Sune F Nielsen ; Henrik Flyger ; Børge G Nordestgaard ; Roger L Milne ; Javier Benítez ; José-Ignacio Arias-Pérez ; M Pilar Zamora ; Hoda Anton-Culver ; Argyrios Ziogas ; Leslie Bernstein ; Christina Clarke Dur ; Hermann Brenner ; Heiko Müller ; Volker Arndt ; Anne Langheinz ; Alfons Meindl ; Michael Golatta ; Claus R Bartram ; Rita K Schmutzler ; Hiltrud Brauch ; Christina Justenhoven ; Thomas Brüning ; GENICA Network ; Jenny Chang-Claude ; Shan Wang-Gohrke ; Ursula Eilber ; Thilo Dörk ; Peter Schürmann ; Michael Bremer ; Peter Hillemanns ; Heli Nevanlinna ; Taru A Muranen ; Kristiina Aittomäki ; Carl Blomqvist ; Natalia Bogdanova ; Natalia Antonenkova ; Yuriy Rogov ; Marina Bermisheva ; Darya Prokofyeva ; Guzel Zinnatullina ; Elza Khusnutdinova ; Annika Lindblom ; Sara Margolin ; Arto Mannermaa ; Veli-Matti Kosma ; Jaana M Hartikainen ; Vesa Kataja ; Georgia Chenevix-Trench ; Jonathan Beesley ; Xiaoqing Chen ; kConFab Investigators ; Australian Ovarian Cancer Study Group ; Diether Lambrechts ; Ann Smeets ; Robert Paridaens ; Caroline Weltens ; Dieter Flesch-Janys ; Katharina Buck ; Sabine Behrens ; Paolo Peterlongo ; Loris Bernard ; Siranoush Manoukian ; Paolo Radice ; Fergus J Couch ; Celine Vachon ; Xianshu Wang ; Janet Olson ; Graham Giles ; Laura Baglietto ; Cariona A McLean ; Gianluca Severi ; Esther M John ; Alexander Miron ; Robert Winqvist ; Katri Pylkäs ; Arja Jukkola-Vuorinen ; Mervi Grip ; Irene L Andrulis ; Julia A Knight ; Anna Marie Mulligan ; Nayana Weerasooriya ; Peter Devilee ; Robert AEM Tollenaar ; John WM Martens ; Caroline M Seynaeve ; Maartje J Hooning ; Antoinette Hollestelle ; Agnes Jager ; Madeleine MA Tilanus-Linthorst ; Per Hall ; Kamila Czene ; Jianjun Liu ; Jingmei Li ; Angela Cox ; Simon S Cross ; Ian W Brock ; Malcolm WR Reed ; Paul Pharoah ; Fiona M Blows ; Alison M Dunning ; Maya Ghoussaini ; Alan Ashworth ; Anthony Swerdlow ; Michael Jones ; Minouk Schoemaker ; Douglas F Easton ; Manjeet Humphreys ; Qin Wang ; Julian Peto ORCID logo ; Isabel dos-Santos-Silva ORCID logo ; (2012) 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium. Cancer epidemiology, biomarkers & prevention, 21 (10). pp. 1783-1791. ISSN 1055-9965 DOI: 10.1158/1055-9965.EPI-12-0526
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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 × 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 × 10(-143)], but no evidence of ethnic differences in per allele OR (P(het) = 0.43). rs865686 was associated with estrogen receptor-positive (ER(+)) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 × 10(-22)) but less strongly, if at all, with ER-negative (ER(-)) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; P(het) = 1.16 × 10(-6)), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER(+) tumors. 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.
Item Type Article
ISI 309576100022
Date Deposited 08 Aug 2012 05:24

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