Association analysis identifies 65 new breast cancer risk loci.

Authors:
Dr Dylan Glubb, PhD
Dr Dylan Glubb, PhD
QIMR Berghofer Medical Research Institute
Brisbane, QLD | Australia
Kyriaki Michailidou Sara Lindström Joe Dennis Jonathan Beesley Shirley Hui Siddhartha Kar Audrey Lemaçon Penny Soucy Asha Rostamianfar Manjeet K Bolla Qin Wang Jonathan Tyrer Ed Dicks Andrew Lee Zhaoming Wang Jamie Allen Renske Keeman Ursula Eilber Juliet D French Xiao Qing Chen Laura Fachal Karen McCue Amy E McCart Reed Maya Ghoussaini Jason S Carroll Xia Jiang Hilary Finucane Marcia Adams Muriel A Adank Habibul Ahsan Kristiina Aittomäki Hoda Anton-Culver Natalia N Antonenkova Volker Arndt Kristan J Aronson Banu Arun Paul L Auer François Bacot Myrto Barrdahl Caroline Baynes Matthias W Beckmann Sabine Behrens Javier Benitez Marina Bermisheva Leslie Bernstein Carl Blomqvist Natalia V Bogdanova Stig E Bojesen Bernardo Bonanni Anne-Lise Børresen-Dale Judith S Brand Hiltrud Brauch Paul Brennan Hermann Brenner Louise Brinton Per Broberg Ian W Brock Annegien Broeks Angela Brooks-Wilson Sara Y Brucker Thomas Brüning Barbara Burwinkel Katja Butterbach Qiuyin Cai Hui Cai Trinidad Caldés Federico Canzian Angel Carracedo Brian D Carter Jose E Castelao Tsun L Chan Ting-Yuan David Cheng Kee Seng Chia Ji-Yeob Choi Hans Christiansen Christine L Clarke Margriet Collée Don M Conroy Emilie Cordina-Duverger Sten Cornelissen David G Cox Angela Cox Simon S Cross Julie M Cunningham Kamila Czene Mary B Daly Peter Devilee Kimberly F Doheny Thilo Dörk Isabel Dos-Santos-Silva Martine Dumont Lorraine Durcan Miriam Dwek Diana M Eccles Arif B Ekici A Heather Eliassen Carolina Ellberg Mingajeva Elvira Christoph Engel Mikael Eriksson Peter A Fasching Jonine Figueroa Dieter Flesch-Janys Olivia Fletcher Henrik Flyger Lin Fritschi Valerie Gaborieau Marike Gabrielson Manuela Gago-Dominguez Yu-Tang Gao Susan M Gapstur José A García-Sáenz Mia M Gaudet Vassilios Georgoulias Graham G Giles Gord Glendon Mark S Goldberg David E Goldgar Anna González-Neira Grethe I Grenaker Alnæs Mervi Grip Jacek Gronwald Anne Grundy Pascal Guénel Lothar Haeberle Eric Hahnen Christopher A Haiman Niclas Håkansson Ute Hamann Nathalie Hamel Susan Hankinson Patricia Harrington Steven N Hart Jaana M Hartikainen Mikael Hartman Alexander Hein Jane Heyworth Belynda Hicks Peter Hillemanns Dona N Ho Antoinette Hollestelle Maartje J Hooning Robert N Hoover John L Hopper Ming-Feng Hou Chia-Ni Hsiung Guanmengqian Huang Keith Humphreys Junko Ishiguro Hidemi Ito Motoki Iwasaki Hiroji Iwata Anna Jakubowska Wolfgang Janni Esther M John Nichola Johnson Kristine Jones Michael Jones Arja Jukkola-Vuorinen Rudolf Kaaks Maria Kabisch Katarzyna Kaczmarek Daehee Kang Yoshio Kasuga Michael J Kerin Sofia Khan Elza Khusnutdinova Johanna I Kiiski Sung-Won Kim Julia A Knight Veli-Matti Kosma Vessela N Kristensen Ute Krüger Ava Kwong Diether Lambrechts Loic Le Marchand Eunjung Lee Min Hyuk Lee Jong Won Lee Chuen Neng Lee Flavio Lejbkowicz Jingmei Li Jenna Lilyquist Annika Lindblom Jolanta Lissowska Wing-Yee Lo Sibylle Loibl Jirong Long Artitaya Lophatananon Jan Lubinski Craig Luccarini Michael P Lux Edmond S K Ma Robert J MacInnis Tom Maishman Enes Makalic Kathleen E Malone Ivana Maleva Kostovska Arto Mannermaa Siranoush Manoukian JoAnn E Manson Sara Margolin Shivaani Mariapun Maria Elena Martinez Keitaro Matsuo Dimitrios Mavroudis James McKay Catriona McLean Hanne Meijers-Heijboer Alfons Meindl Primitiva Menéndez Usha Menon Jeffery Meyer Hui Miao Nicola Miller Nur Aishah Mohd Taib Kenneth Muir Anna Marie Mulligan Claire Mulot Susan L Neuhausen Heli Nevanlinna Patrick Neven Sune F Nielsen Dong-Young Noh Børge G Nordestgaard Aaron Norman Olufunmilayo I Olopade Janet E Olson Håkan Olsson Curtis Olswold Nick Orr V Shane Pankratz Sue K Park Tjoung-Won Park-Simon Rachel Lloyd Jose I A Perez Paolo Peterlongo Julian Peto Kelly-Anne Phillips Mila Pinchev Dijana Plaseska-Karanfilska Ross Prentice Nadege Presneau Darya Prokofyeva Elizabeth Pugh Katri Pylkäs Brigitte Rack Paolo Radice Nazneen Rahman Gadi Rennert Hedy S Rennert Valerie Rhenius Atocha Romero Jane Romm Kathryn J Ruddy Thomas Rüdiger Anja Rudolph Matthias Ruebner Emiel J T Rutgers Emmanouil Saloustros Dale P Sandler Suleeporn Sangrajrang Elinor J Sawyer Daniel F Schmidt Rita K Schmutzler Andreas Schneeweiss Minouk J Schoemaker Fredrick Schumacher Peter Schürmann Rodney J Scott Christopher Scott Sheila Seal Caroline Seynaeve Mitul Shah Priyanka Sharma Chen-Yang Shen Grace Sheng Mark E Sherman Martha J Shrubsole Xiao-Ou Shu Ann Smeets Christof Sohn Melissa C Southey John J Spinelli Christa Stegmaier Sarah Stewart-Brown Jennifer Stone Daniel O Stram Harald Surowy Anthony Swerdlow Rulla Tamimi Jack A Taylor Maria Tengström Soo H Teo Mary Beth Terry Daniel C Tessier Somchai Thanasitthichai Kathrin Thöne Rob A E M Tollenaar Ian Tomlinson Ling Tong Diana Torres Thérèse Truong Chiu-Chen Tseng Shoichiro Tsugane Hans-Ulrich Ulmer Giske Ursin Michael Untch Celine Vachon Christi J van Asperen David Van Den Berg Ans M W van den Ouweland Lizet van der Kolk Rob B van der Luijt Daniel Vincent Jason Vollenweider Quinten Waisfisz Shan Wang-Gohrke Clarice R Weinberg Camilla Wendt Alice S Whittemore Hans Wildiers Walter Willett Robert Winqvist Alicja Wolk Anna H Wu Lucy Xia Taiki Yamaji Xiaohong R Yang Cheng Har Yip Keun-Young Yoo Jyh-Cherng Yu Wei Zheng Ying Zheng Bin Zhu Argyrios Ziogas Elad Ziv Sunil R Lakhani Antonis C Antoniou Arnaud Droit Irene L Andrulis Christopher I Amos Fergus J Couch Paul D P Pharoah Jenny Chang-Claude Per Hall David J Hunter Roger L Milne Montserrat García-Closas Marjanka K Schmidt Stephen J Chanock Alison M Dunning Stacey L Edwards Gary D Bader Georgia Chenevix-Trench Jacques Simard Peter Kraft Douglas F Easton

Nature 2017 11 23;551(7678):92-94. Epub 2017 Oct 23.

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

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http://dx.doi.org/10.1038/nature24284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798588PMC
November 2017
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(Supplied by CrossRef)
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J Long et al.
PLoS Genet. 2012
Article in Nat. Genet.
Q Cai et al.
Nat. Genet. 2014
Article in J. Natl Cancer Inst.
J Long et al.
J. Natl Cancer Inst. 2013
Article in Nat. Genet.
C He et al.
Nat. Genet. 2009
Article in Cell
T Kawase et al.
Cell 2009
Article in Genome Res.
O Corradin et al.
Genome Res. 2014
Article in Proc. Natl Acad. Sci. USA
B He et al.
Proc. Natl Acad. Sci. USA 2014
Article in Nature
R Andersson et al.
Nature 2014
Article in Nature
S Nik-Zainal et al.
Nature 2016

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