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

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• 作者：Jiajun Shi ; Yanfeng Zhang ; Wei Zheng ; Kyriaki Michailidou ; Maya Ghoussaini ; Manjeet K. Bolla ; Qin 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 Benitez ; Alicia Beeghly-Fadiel ; William Blot ; Natalia V. Bogdanova ; Stig E. Bojesen ; Hiltrud Brauch ; Hermann Brenner ; Louise Brinton ; Annegien Broeks ; Thomas Brü ; ning ; 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 Dork ; Peter A. Fasching ; Olivia Fletcher ; Henrik Flyger ; Florentia Fostira ; Valerie Gaborieau ; Montserrat Garcí ; a-Closas ; Graham G. Giles ; Mervi Grip ; Pascal Guenel ; Christopher A. Haiman ; Ute Hamann ; Mikael Hartman ; Hui Miao ; Antoinette Hollestelle ; John L. Hopper ; Chia-Ni Hsiung ; kConFab Investigators ; 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 Lubinski ; Arto Mannermaa ; Siranoush Manoukian ; Loic Le Marchand ; Sara Margolin ; Frederik Marme ; Keitaro Matsuo ; Catriona McLean ; Alfons Meindl ; Kenneth Muir ; Susan L. Neuhausen ; Heli Nevanlinna ; Silje Nord ; Anne-Lise Bø ; rresen-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 Swerdlow ; Soo Hwang Teo ; Bernard Thienpont ; Amanda E. Toland ; Robert A.E.M. Tollenaar ; Ian Tomlinson ; Therese Truong ; Chiu-chen Tseng ; Wanqing Wen ; Robert Winqvist ; Anna H. Wu ; Cheng Har Yip ; Pilar M. 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 and Jirong Long
• 刊名：International Journal of Cancer
• 出版年：2016
• 出版时间：15 September 2016
• 年：2016
• 卷：139
• 期：6
• 页码：1303-1317
• 全文大小：3937K
• ISSN：1097-0215

文摘

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, r² = 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.