Association analysis identifies 65 new breast cancer risk loci

@article{Michailidou2017AssociationAI,
  title={Association analysis identifies 65 new breast cancer risk loci},
  author={Kyriaki Michailidou and Sara Lindstr{\"o}m and Joe G. Dennis and Jonathan Beesley and Shirley Hui and Siddhartha P. Kar and Audrey Lemaçon and Penny Soucy and Dylan M Glubb and Asha Rostamianfar and Manjeet K. Bolla and Qin Wang and Jonathan P. Tyrer and E. Dicks and Andrew Lee and Zhaoming Wang and Jamie Allen and Renske Keeman and Ursula Eilber and Juliet D. French and Xiao Qing Chen and Laura Fachal and Karen McCue and Amy E. McCart Reed and Maya Ghoussaini and Jason S. Carroll and Xia Jiang and Hilary K. Finucane and Marcia Adams and Muriel A. Adank and Habibul Ahsan and Kristiina Aittom{\"a}ki and Hoda Anton-Culver and Natalia N. Antonenkova and Volker Arndt and Kristan J Aronson and Banu K Arun and Paul L. Auer and François Bacot and Myrto Barrdahl and Caroline Baynes and Matthias Wilhelm Beckmann and Sabine Behrens and Javier Ben{\'i}tez and Marina A. Bermisheva and Leslie Bernstein and Carl Blomqvist and Natalia V Bogdanova and Stig Egil Bojesen and Bernardo Bonanni and Anne-Lise B{\o}rresen-Dale and Judith S. Brand and Hiltrud Brauch and Paul J Brennan and Hermann Brenner and Louise A. Brinton and Per Broberg and Ian Wallace Brock and Annegien Broeks and Angela R. Brooks-Wilson and Sara Yvonne Brucker and Thomas Br{\"u}ning and Barbara Burwinkel and Katja Butterbach and Qiuyin Cai and Hui Cai and Trinidad Cald{\'e}s and Federico Canzian and {\'A}ngel Carracedo and Brian Carter and Jos{\'e} Esteban Castelao and T. L. Chan and Ting-Yuan David Cheng and Kee Seng Chia and Ji-Yeob Choi and Hans Christiansen and Christine L. Clarke and Margriet Collee and Don M. Conroy and Emilie Cordina-Duverger and Sten Cornelissen and David G. Cox and Angela Cox and Simon S. Cross and Julie M. Cunningham and Kamila Czene and Mary B Daly and Peter Devilee and Kimberly F. Doheny and Thilo D{\"o}rk and Isabel Dos-Santos-Silva and Martine Dumont and Lorraine Durcan and Miriam V. Dwek and Diana M. Eccles and Arif B{\"u}lent Ekici and A. Heather Eliassen and Carolina Ellberg and Mingajeva Elvira and Christoph Engel and Mikael Eriksson and Peter Andreas Fasching and Jonine D. Figueroa and Dieter Flesch‐Janys and Olivia Fletcher and Henrik Flyger and Lin Fritschi and Valerie Gaborieau and Marike Gabrielson and Manuela Gago-Dom{\'i}nguez and Yu-Tang Gao and Susan M Gapstur and Jos{\'e} Angel Garc{\'i}a-Saenz and Mia M. Gaudet and Vassilios Georgoulias and Graham G. Giles and Gord Glendon and Mark S. Goldberg and David E. Goldgar and Anna Gonz{\'a}lez-Neira and Grethe I. Grenaker Aln{\ae}s and Mervi Grip and Jacek Gronwald and Anne Grundy and Pascal Gu{\'e}nel and Lothar Haeberle and Eric Hahnen and Christopher A. Haiman and Niclas H{\aa}kansson and Ute Hamann and Nathalie J. Hamel and Susan E Hankinson and Patricia A. Harrington and Steven N. Hart and Jaana M. Hartikainen and Mikael Hartman and Alexander Hein and Jane S. Heyworth and Belynda D. Hicks and Peter Hillemanns and Dona N. Ho and Antoinette Hollestelle and Maartje J. Hooning and Robert N Hoover and John L. Hopper and Ming-Feng Hou and Chia-Ni Hsiung and Guanmengqian Huang and Keith Humphreys and Junko Ishiguro and Hidemi Ito and Motoki Iwasaki and Hiroji Iwata and Anna Jakubowska and Wolfgang Janni and Esther M. John and Nichola Johnson and Kristine Jones and Michael E. Jones and Arja Jukkola-Vuorinen and Rudolf Kaaks and Maria Kabisch and Katarzyna Kaczmarek and Daehee Kang and Yoshio Kasuga and Michael J. Kerin and Sofia Khan and Elza K. Khusnutdinova and Johanna I. Kiiski and Sung-Won Kim and Julia A Knight and V. M. Kosma and Vessela N. Kristensen and Ute Kr{\"u}ger and Ava Kwong and Diether Lambrechts and Loic Le Marchand and Eunjung Lee and Min Hyuk Lee and Jong Won Lee and Chuen Neng Lee and Flavio Lejbkowicz and Jingmei Li and Jenna Lilyquist and Annika Lindblom and Jolanta Lissowska and Wing-Yee Lo and Sibylle Loibl and Jirong Long and Artitaya Lophatananon and Jan Lubiński and Craig Luccarini and Michael Patrick Lux and Edmond S. K. Ma and Robert J. MacInnis and Tom Maishman and Enes Makalic and Kathleen E. Malone and Ivana Maleva Kostovska and Arto Mannermaa and Siranoush Manoukian and JoAnn E. Manson and Sara Margolin and Shivaani Mariapun and Mar{\'i}a Elena Mart{\'i}nez and Keitaro Matsuo and Dimitrios Mavroudis and James Mckay and Catriona Mclean and Hanne Meijers-Heijboer and Alfons Meindl and Primitiva Men{\'e}ndez and Usha Menon and Jeffery M. Meyer and Hui Miao and Nicola Miller and Nur Aishah Mohd Taib and Kenneth Ross Muir and Anna Marie Mulligan and Claire Mulot and Susan L. Neuhausen and Heli Nevanlinna and Patrick Neven and Sune Fallgaard Nielsen and Dong-Young Noh and B{\o}rge Gr{\o}nne Nordestgaard and Aaron D Norman and Olufunmilayo I. Olopade and Janet E. Olson and H{\aa}kan Olsson and Curtis L. Olswold and Nick Orr and Vernon S Pankratz and Sue-Kyung Park and Tjoung-Won Park-Simon and Rachel Malchow Lloyd and Jos{\'e} Ignacio Arias P{\'e}rez and Paolo Peterlongo and Julian Peto and Kelly-Anne Phillips and Mila Pinchev and Dijana Plaseska-Karanfilska and Ross L. Prentice and Nad{\'e}ge Presneau and Darya Prokofieva and Elizabeth Pugh and Katri Pylk{\"a}s and Brigitte K. Rack and Paolo Radice and Nazneen Rahman and Gadi Rennert and Hedy S. Rennert and Valerie Rhenius and Atocha Romero and Jane M. Romm and Kathryn J. Ruddy and Thomas R{\"u}diger and Anja Rudolph and Matthias Ruebner and Emiel J. Th. Rutgers and Emmanouil Saloustros and Dale P. Sandler and Suleeporn Sangrajrang and Elinor J. Sawyer and Daniel F. Schmidt and Rita Schmutzler and Andreas Schneeweiss and Minouk J Schoemaker and Fredrick R. Schumacher and Peter Schürmann and Rodney J. Scott and Christopher Scott and Sheila Seal and Caroline M. Seynaeve and Mitul Shah and Priyanka Sharma and Chen-Yang Shen and Grace Sheng and Mark E. Sherman and Martha J. Shrubsole and Xiao-Ou Shu and Ann Smeets and Christof Sohn and Melissa C. Southey and John J. Spinelli and Christa Stegmaier and Sarah Stewart-Brown and Jennifer Stone and Daniel O. Stram and Harald M Surowy and Anthony J. Swerdlow and Rulla M. Tamimi and Jack A. Taylor and Maria Tengstr{\"o}m and Soo-Hwang Teo and Mary Beth Terry and Daniel C. Tessier and Somchai Thanasitthichai and Kathrin Th{\"o}ne and Rob Aem Tollenaar and Ian P. M. Tomlinson and Ling Tong and Diana Torres and Th{\'e}r{\`e}se Truong and Chiu‐chen Tseng and Shoichiro Tsugane and Hans Ulrich Ulmer and Giske Ursin and Michael Untch and Celine M. Vachon and Christi J. van Asperen and David J. Van Den Berg and Ans M. W. van den Ouweland and Lizet van der Kolk and Rob B van der Luijt and Daniel Vincent and Jason Vollenweider and Quinten Waisfisz and Shan Wang-gohrke and Clarice R. Weinberg and Camilla Wendt and Alice S. Whittemore and Hans Wildiers and Walter C. Willett and Robert Winqvist and Alicja Wolk and Anna H Wu and Lucy Y. Xia and Taiki Yamaji and Xiaohong R. Yang and Cheng Har Yip and Keun-Young Yoo and Jyh‐cherng Yu and Wei Zheng and Ying Zheng and Bin Zhu and Argyrios Ziogas and Elad Ziv and Sunil R. Lakhani and Antonis C. Antoniou and Arnaud Droit and Irene L. Andrulis and Christopher I. Amos and Fergus J. Couch and Paul D. P. Pharoah and Jenny Chang-Claude and Per Hall and David J. Hunter and Roger L. Milne and Montserrat Garc{\'i}a-Closas and Marjanka K. Schmidt and Stephen J. Chanock and Alison M. Dunning and Stacey L. Edwards and Gary D Bader and Georgia Chenevix-Trench and Jacques Simard and Peter Kraft and Douglas F. Easton},
  journal={Nature},
  year={2017},
  volume={551},
  pages={92 - 94}
}
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… 

A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

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Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

A genome-wide association study including 133,384 breast cancer cases and 113,789 controls plus 18,908 BRCA1 mutation carriers of European ancestry provides an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

It is hypothesized that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen, using expression quantitative trait loci reported in these tissues to identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function.

Identifying 31 novel breast cancer susceptibility loci using data from genome-wide association studies conducted in Asian and European women

A meta-analysis of data from genome-wide association studies conducted in Asians found variants showing an association with breast cancer risk at P.

Common breast cancer risk loci predispose to distinct tumor subtypes

About half of the breast cancer susceptibility loci discovered in overall and ER-specific risk analyses have differential associations with clinical tumor features, providing insights into the genetic predisposition of breast cancer subtypes and can inform subtype- specific risk prediction.

Common Genetic Variation and Breast Cancer Risk—Past, Present, and Future

Findings associated with overall breast cancer, pathologic subtypes, and mutation carriers (BRCA1, BRCA2, and CHEK2) are summarized and the development of polygenic risk scores (PRS) using the risk-associated SNPs are summarized to show how PRS can contribute to estimation of individual risks for developing breast cancer.

Potential Misrepresentation of Inherited Breast Cancer Risk by Common Germline Alleles

The results support the genetic heterogeneity and rare-variant/haplotype basis of breast cancer risk and suggest a novel type of "synthetic association" wherein common risk alleles on a rare risk haplotype may misrepresent disease risk through their tagging of many "false positive" haplotypes.
...

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