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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

2016; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/ncomms10979

2041-1723

Alexander Gusev, Huwenbo Shi, Gleb Kichaev, Mark M. Pomerantz, Fugen Li, Henry W. Long, Sue A. Ingles, Rick A. Kittles, Sara S. Strom, Benjamin A. Rybicki, Barbara Nemesure, William B. Isaacs, Wei Zheng, Curtis A. Pettaway, Edward D. Yeboah, Yao Tettey, Richard Biritwum, Andrew A. Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Anand P. Chokkalingam, Esther M. John, Adam B. Murphy, Lisa B. Signorello, John D. Carpten, M. Cristina Leske, Suh-Yuh Wu, Anslem J. M. Hennis, Christine Neslund‐Dudas, Ann W. Hsing, Lisa W. Chu, Phyllis J. Goodman, Eric A. Klein, John S. Witte, Graham Casey, Sam Kaggwa, Michael B. Cook, Daniel O. Stram, William J. Blot, Rosalind A. Eeles, Douglas F. Easton, Zsofia Kote‐Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G. Giles, Melissa C. Southey, Liesel M. FitzGerald, Henrik Grönberg, Fredrik Wiklund, Markus Aly, Brian E. Henderson, Johanna Schleutker, Tiina Wahlfors, Teuvo L.J. Tammela, Børge G. Nordestgaard, Tim Key, Ruth C. Travis, David E. Neal, Jenny Donovan, Freddie C. Hamdy, Paul D.P. Pharoah, Nora Pashayan, Kay‐Tee Khaw, Janet L. Stanford, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Christiane Maier, Walther Vogel, Manuel Luedeke, Kathleen Herkommer, Adam S. Kibel, Cezary Cybulski, Dominika Wokołorczyk, Wojciech Kluźniak, Lisa Cannon‐Albright, Craig C. Teerlink, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Jong Y. Park, Thomas A. Sellers, Hui‐Yi Lin, Chavdar Slavov, Radka Kaneva, Vanio Mitev, Jyotsna Batra, Amanda B. Spurdle, Judith A. Clements, Manuel R. Teixeira, Hardev Pandha, Agnieszka Michael, Paula Paulo, Sofia Maia, Andrzej Kierzek, Margaret Cook, Michelle Guy, Koveela Govindasami, Daniel Leongamornlert, Emma Sawyer, Rosemary Wilkinson, Edward J. Saunders, Malgorzata Tymrakiewicz, Tokhir Dadaev, Angela Morgan, Cyril Fisher, Steve Hazel, Naomi Livni, Artitaya Lophatananon, John Pedersen, John L. Hopper, Jan Adolfson, P Stattin, Jan-Erik Johansson, Carin Cavalli-Bjoerkman, Ami Karlsson, Michael Broms, Anssi Auvinen, Paula Kujala, Liisa Maeaettaenen, Teemu Murtola, Kimmo Taari, Maren Weischer, Sune F. Nielsen, Peter Klarskov, Martin Andreas Røder, Peter Kr. Iversen, Hans Wallinder, Sven A. Gustafsson, Angela Cox, Paul Brown, Anne George, Gemma Marsden, J. Athene Lane, Michael S. Davis, Wei Zheng, Lisa B. Signorello, William J. Blot, Lori S. Tillmans, Shaun M. Riska, Liang Wang, Antje E. Rinckleb, Jan Lubiski, Christa Stegmaier, Julio M. Pow‐Sang, Hyun Park, Selina Radlein, Maria Rincon, James Haley, Babu Zachariah, Darina Kachakova, Elenko Popov, A. Mitkova, A. Vlahova, Tihomir Dikov, S. Christova, Peter Heathcote, Glenn Wood, Greg Malone, Pâmela Saunders, Allison Eckert, Trina Yeadon, Kris Kerr, Angus Collins, Megan Turner, Srilakshmi Srinivasan, Mary‐Anne Kedda, Kimberly Alexander, Tracy A. O’Mara, Huihai Wu, Rui Henrique, Pedro Pinto, Joana Santos, João D. Barros‐Silva, David V. Conti, Demetrius Albanes, Christine D. Berg, Sonja I. Berndt, Daniele Campa, E. David Crawford, W. Ryan Diver, Susan M. Gapstur, J. Michael Gaziano, Edward Giovannucci, Robert N. Hoover, David J. Hunter, Mattias Johansson, Peter Kraft, Loı̈c Le Marchand, Sara Lindström, Carmen Navarro, Kim Overvad, Elio Ríboli, Afshan Siddiq, Victoria L. Stevens, Dimitrios Trichopoulos, Paolo Vineis, Meredith Yeager, Gosia Trynka, Soumya Raychaudhuri, Fredrick R. Schumacher, Alkes L. Price, Matthew L. Freedman, Christopher A. Haiman, Bogdan Paşaniuc,

Prostate Cancer Diagnosis and Treatment

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.