Fine‐scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer
Authors: Shi Jiajun , Zhang Yanfeng , Zheng Wei , Michailidou Kyriaki , Ghoussaini Maya , Bolla Manjeet K. , Wang Qin , Dennis Joe , Lush Michael , Milne Roger L. , Shu Xiao‐Ou , Beesley Jonathan , Kar Siddhartha , Andrulis Irene L. , Anton‐Culver Hoda , Arndt Volker , Beckmann Matthias W. , Zhao Zhiguo , Guo Xingyi , Benitez Javier , Beeghly‐Fadiel Alicia , Blot William , Bogdanova Natalia V. , Bojesen Stig E. , Brauch Hiltrud , Brenner Hermann , Brinton Louise , Broeks Annegien , Brüning Thomas , Burwinkel Barbara , Cai Hui , Canisius Sander , Chang‐Claude Jenny , Choi Ji‐Yeob , Couch Fergus J. , Cox Angela , Cross Simon S. , Czene Kamila , Darabi Hatef , Devilee Peter , Droit Arnaud , Dork Thilo , Fasching Peter A. , Fletcher Olivia , Flyger Henrik , Fostira Florentia , Gaborieau Valerie , García‐Closas Montserrat , Giles Graham G. , Grip Mervi , Guenel Pascal , Haiman Christopher A. , Hamann Ute , Hartman Mikael , Miao Hui , Hollestelle Antoinette , Hopper John L. , Hsiung Chia‐Ni ,   kConFab Investigators, Ito Hidemi , Jakubowska Anna , Johnson Nichola , Torres Diana , Kabisch Maria , Kang Daehee , Khan Sofia , Knight Julia A. , Kosma Veli‐Matti , Lambrechts Diether , Li Jingmei , Lindblom Annika , Lophatananon Artitaya , Lubinski Jan , Mannermaa Arto , Manoukian Siranoush , Le Marchand Loic , Margolin Sara , Marme Frederik , Matsuo Keitaro , McLean Catriona , Meindl Alfons , Muir Kenneth , Neuhausen Susan L. , Nevanlinna Heli , Nord Silje , Børresen‐Dale Anne‐Lise , Olson Janet E. , Orr Nick , van den Ouweland Ans M.W. , Peterlongo Paolo , Choudary Putti Thomas , Rudolph Anja , Sangrajrang Suleeporn , Sawyer Elinor J. , Schmidt Marjanka K. , Schmutzler Rita K. , Shen Chen‐Yang , Hou Ming‐Feng , Shrubsole Matha J. , Southey Melissa C. , Swerdlow Anthony , Hwang Teo Soo , Thienpont Bernard , Toland Amanda E. , Tollenaar Robert A.E.M. , Tomlinson Ian , Truong Therese , Tseng Chiu‐chen , Wen Wanqing , Winqvist Robert , Wu Anna H. , Har Yip Cheng , Zamora Pilar M. , Zheng Ying , Floris Giuseppe , Cheng Ching‐Yu , Hooning Maartje J. , Martens John W.M. , Seynaeve Caroline , Kristensen Vessela N. , Hall Per , Pharoah Paul D.P. , Simard Jacques , Chenevix‐Trench Georgia , Dunning Alison M. , Antoniou Antonis C. , Easton Douglas F. , Cai Qiuyin , Long Jirong 
Published: April 2016

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.