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Fine‐scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer

2016; Wiley; Volume: 139; Issue: 6 Linguagem: Inglês

10.1002/ijc.30150

1097-0215

Jiajun Shi, Yanfeng Zhang, Wei Zheng, Kyriaki Michailidou, Maya Ghoussaini, Manjeet K. Bolla, Sophia Wang, Joe Dennis, Michael Lush, Roger L. Milne, Xiao‐Ou Shu, Jonathan Beesley, Siddhartha Kar, Irene L. Andrulis, Hoda Anton‐Culver, Volker Arndt, Matthias W. Beckmann, Zhiguo Zhao, Xingyi Guo, Javier Benı́tez, Alicia Beeghly‐Fadiel, William J. Blot, Natalia Bogdanova, Stig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Louise A. Brinton, Annegien Broeks, Thomas Brüning, Barbara Burwinkel, Hui Cai, Sander Canisius, Jenny Chang‐Claude, Ji‐Yeob Choi, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Hatef Darabi, Peter Devilee, Arnaud Droit, Thilo Dörk, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Florentia Fostira, Valérie Gaborieau, Montserrat García‐Closas, Graham G. Giles, Mervi Grip, Pascal Guénel, Christopher A. Haiman, Ute Hamann, Mikael Hartman, Hui Miao, Antoinette Hollestelle, John L. Hopper, Chia‐Ni Hsiung, Hidemi Ito, Anna Jakubowska, Nichola Johnson, Diana Torres, Maria Kabisch, Daehee Kang, Sofia Khan, Julia A. Knight, Veli‐Matti Kosma, Diether Lambrechts, Jingmei Li, Annika Lindblom, Artitaya Lophatananon, Jan Lubiński, Arto Mannermaa, Siranoush Manoukian, Loı̈c Le Marchand, Sara Margolin, Frederik Marmé, Keitaro Matsuo, Catriona McLean, Thomas Ind, Kenneth Muir, Susan L. Neuhausen, Heli Nevanlinna, Silje Nord, Anne‐Lise Børresen‐Dale, Janet E. Olson, Nick Orr, Ans M.W. van den Ouweland, Paolo Peterlongo, Thomas Choudary Putti, Anja Rudolph, Suleeporn Sangrajrang, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Chen‐Yang Shen, Ming‐Feng Hou, Matha J. Shrubsole, Melissa C. Southey, Anthony J. Swerdlow, Soo‐Hwang Teo, Bernard Thienpont, Amanda E. Toland, Robert A.E.M. Tollenaar, Ian Tomlinson, Thérèse Truong, Chiu-Chen Tseng, Wanqing Wen, Robert Winqvist, Anna H. Wu, Cheng Har Yip, Pilar Zamora, Ying Zheng, Giuseppe Floris, Ching‐Yu Cheng, Maartje J. Hooning, John W.M. Martens, Caroline Seynaeve, Vessela N. Kristensen, Per Hall, Paul D.P. Pharoah, Jacques Simard, Georgia Chenevix‐Trench, Alison M. Dunning, Antonis C. Antoniou, Douglas F. Easton, Qiuyin Cai, Jirong Long,

Genomics and Chromatin Dynamics

Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2) = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.