| Literature DB >> 26073781 |
Hatef Darabi1, Karen McCue2, Jonathan Beesley2, Kyriaki Michailidou3, Silje Nord4, Siddhartha Kar5, Keith Humphreys1, Deborah Thompson3, Maya Ghoussaini5, Manjeet K Bolla3, Joe Dennis3, Qin Wang3, Sander Canisius6, Christopher G Scott7, Carmel Apicella8, John L Hopper8, Melissa C Southey9, Jennifer Stone10, Annegien Broeks6, Marjanka K Schmidt6, Rodney J Scott11, Artitaya Lophatananon12, Kenneth Muir13, Matthias W Beckmann14, Arif B Ekici15, Peter A Fasching16, Katharina Heusinger14, Isabel Dos-Santos-Silva17, Julian Peto17, Ian Tomlinson18, Elinor J Sawyer19, Barbara Burwinkel20, Frederik Marme21, Pascal Guénel22, Thérèse Truong22, Stig E Bojesen23, Henrik Flyger24, Javier Benitez25, Anna González-Neira26, Hoda Anton-Culver27, Susan L Neuhausen28, Volker Arndt29, Hermann Brenner30, Christoph Engel31, Alfons Meindl32, Rita K Schmutzler33, Norbert Arnold34, Hiltrud Brauch35, Ute Hamann36, Jenny Chang-Claude37, Sofia Khan38, Heli Nevanlinna38, Hidemi Ito39, Keitaro Matsuo40, Natalia V Bogdanova41, Thilo Dörk42, Annika Lindblom43, Sara Margolin44, Veli-Matti Kosma45, Arto Mannermaa45, Chiu-Chen Tseng46, Anna H Wu46, Giuseppe Floris47, Diether Lambrechts48, Anja Rudolph37, Paolo Peterlongo49, Paolo Radice50, Fergus J Couch51, Celine Vachon7, Graham G Giles52, Catriona McLean53, Roger L Milne52, Pierre-Antoine Dugué54, Christopher A Haiman46, Gertraud Maskarinec55, Christy Woolcott56, Brian E Henderson46, Mark S Goldberg57, Jacques Simard58, Soo H Teo59, Shivaani Mariapun59, Åslaug Helland60, Vilde Haakensen61, Wei Zheng62, Alicia Beeghly-Fadiel62, Rulla Tamimi63, Arja Jukkola-Vuorinen64, Robert Winqvist65, Irene L Andrulis66, Julia A Knight67, Peter Devilee68, Robert A E M Tollenaar69, Jonine Figueroa70, Montserrat García-Closas71, Kamila Czene1, Maartje J Hooning72, Madeleine Tilanus-Linthorst73, Jingmei Li74, Yu-Tang Gao75, Xiao-Ou Shu62, Angela Cox76, Simon S Cross77, Robert Luben78, Kay-Tee Khaw79, Ji-Yeob Choi80, Daehee Kang81, Mikael Hartman82, Wei Yen Lim83, Maria Kabisch36, Diana Torres84, Anna Jakubowska85, Jan Lubinski85, James McKay86, Suleeporn Sangrajrang87, Amanda E Toland88, Drakoulis Yannoukakos89, Chen-Yang Shen90, Jyh-Cherng Yu91, Argyrios Ziogas27, Minouk J Schoemaker92, Anthony Swerdlow93, Anne-Lise Borresen-Dale94, Vessela Kristensen95, Juliet D French2, Stacey L Edwards2, Alison M Dunning5, Douglas F Easton96, Per Hall1, Georgia Chenevix-Trench97.
Abstract
Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer.Entities:
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Year: 2015 PMID： 26073781 PMCID： PMC4572510 DOI： 10.1016/j.ajhg.2015.05.002
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025