Germline variation at 8q24 and prostate cancer risk in men of European ancestry
Journal article
Matejcic, Marco, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Wang, Kan, Sheng, Xin, Olama, Ali Amin Al, Schumacher, Fredrick R., Ingles, Sue A., Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I., Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L., Gapstur, Susan M., Tangen, Catherine M., Batra, Jyotsna, ... Haiman, Christopher A.. (2018). Germline variation at 8q24 and prostate cancer risk in men of European ancestry. Nature Communications. 9(1), p. Article 4616. https://doi.org/10.1038/s41467-018-06863-1
Authors | Matejcic, Marco, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Wang, Kan, Sheng, Xin, Olama, Ali Amin Al, Schumacher, Fredrick R., Ingles, Sue A., Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I., Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L., Gapstur, Susan M., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Géraldine, Sorensen, Karina D., Maehle, Lovise, Grindedal, Eli M., Strom, Sara S., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Bensen, Jeanette T., Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A., Pandha, Hardev, Thibodeau, Stephen N., Schaid, Daniel J., Henderson, Brian E., Stern, Mariana C., Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Cook, Margaret, Fachal, Laura, Weinstein, Stephanie, Beane Freeman, Laura E., Hoover, Robert N., Machiela, Mitchell J., Lophatananon, Artitaya, Carter, Brian D., Goodman, Phyllis J., Moya, Leire, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Yeadon, Trina, Eckert, Allison, Eklund, Martin, Cavalli-Bjoerkman, Carin, Dunning, Alison M., Sipeky, Csilla, Hakansson, Niclas, Elliott, Rebecca, Ranu, Hardeep, Giovannucci, Edward, Turman, Constance, Hunter, David J., Cussenot, Olivier, Orntoft, Torben Falck, Lane, Athene, Lewis, Sarah J., Davis, Michael, Key, Tim J., Brown, Paul, Kulkarni, Girish S., Zlotta, Alexandre R., Fleshner, Neil E., Finelli, Antonio, Mao, Xueying, Marzec, Jacek, MacInnis, Robert J., Milne, Roger, Hopper, John L., Aguado, Miguel, Bustamante, Mariona, Castaño-Vinyals, Gemma, Gracia-Lavedan, Esther, Cecchini, Lluís, Stampfer, Meir, Ma, Jing, Sellers, Thomas A., Geybels, Milan S., Park, Hyun, Zachariah, Babu, Kolb, Suzanne, Wokolorczyk, Dominika, Lubinski, Jan, Kluzniak, Wojciech, Nielsen, Sune F., Weisher, Maren, Cuk, Katarina, Vogel, Walther, Luedeke, Manuel, Logothetis, Christopher J. J., Paulo, Paula, Cardoso, Marta, Maia, Sofia, Silva, Maria P., Steele, Linda, Ding, Yuan Chun, De Meerleer, Gert, De Langhe, Sofie, Thierens, Hubert, Lim, Jasmine, Tan, Meng H., Ong, Aik T., Lin, Daniel W., Kachakova, Darina, Mitkova, Atanaska, Mitev, Vanio, Parliament, Matthew, Jenster, Guido, Bangma, Christopher, Schroder, F. H., Truong, Thérèse, Koudou, Yves Akoli, Michael, Agnieszka, Kierzek, Andrzej, Karlsson, Ami, Broms, Michael, Wu, Huihai, Aukim-Hastie, Claire, Tillmans, Lori, Riska, Shaun, McDonnell, Shannon K., Dearnaley, David, Spurdle, Amanda, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Papargiris, Melissa, Saunders, Pamela, Kujala, Paula, Talala, Kirsi, Taari, Kimmo, Bentzen, Søren, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, George, Anne, Toi, Ants, Evans, Andrew, van der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Zhao, Shan-Chao, Ren, Guoping, Zhang, Yangling, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Pedersen, John, Lobato-Busto, Ramón, Ruiz-Dominguez, José Manuel, Mengual, Lourdes, Alcaraz, Antonio, Pow-Sang, Julio, Herkommer, Kathleen, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Adolfsson, Jan, Stattin, Par, Johansson, Jan-Erik, Martin, Richard M., Thompson, Ian M., Chambers, Suzanne, Aitken, Joanne, Horvath, Lisa, Haynes, Anne-Maree, Tilley, Wayne, Risbridger, Gail, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Tammela, Teuvo L. J., Murtola, Teemu, Auvinen, Anssi, Burnet, Neil, Barnett, Gill, Andriole, Gerald, Klim, Aleksandra, Drake, Bettina F., Borre, Michael, Kerns, Sarah, Ostrer, Harry, Zhang, Hong-Wei, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Feng, Ninghan, Li, Jie, He, Weiyang, Guo, Xin, Sun, Zan, Wang, Guomin, Guo, Jianming, Southey, Melissa C., Fitzgerald, Liesel M., Marsden, Gemma, Gómez-Caamaño, Antonio, Carballo, Ana, Peleteiro, Paula, Calvo, Patricia, Szulkin, Robert, Llorca, Javier, Dierssen-Sotos, Trinidad, Gómez Acebo, Inés, Lin, Hui-Yi, Ostrander, Elaine A., Bisbjerg, Rasmus, Klarskov, Peter, Røder, Martin Andreas, Iversen, Peter, Holleczek, Bernd, Stegmaier, Christa, Schnoeller, Thomas, Bohnert, Philipp, John, Esther M., Ost, Piet, Teo, Soo-Hwang, Gamulin, Marija, Kulis, Tomislav, Kastelan, Zeljko, Slavov, Chavdar, Popov, Elenko, Van den Broeck, Thomas, Joniau, Steven, Larkin, Samantha, Castelao, Jose Esteban, Martinez, Maria Elena, van Schaik, Ron H. N., Xu, Jianfeng, Lindström, Sara, Riboli, Elio, Berry, Clare, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Freedman, Matthew, Cenee, Sylvie, Sanchez, Marie, Wiklund, Fredrik, Chanock, Stephen J., Easton, Douglas F., Eeles, Rosalind A., Kote-Jarai, Zsofia, Conti, David V. and Haiman, Christopher A. |
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Abstract | Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification. |
Year | 2018 |
Journal | Nature Communications |
Journal citation | 9 (1), p. Article 4616 |
Publisher | Nature Publishing Group |
ISSN | 2041-1723 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/s41467-018-06863-1 |
Scopus EID | 2-s2.0-85056250910 |
Open access | Published as ‘gold’ (paid) open access |
Page range | 1-11 |
Funder | National Institutes of Health (NIH), United States of America |
Cancer Research UK | |
European Commission | |
Institute of Cancer Research | |
Prostate Cancer Research Foundation | |
Prostate Research Campaign UK | |
Orchid Cancer Appeal | |
National Cancer Research Network UK | |
National Cancer Research Institute (NCRI) UK | |
National Institute for Health Research (NIHR) | |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 05 Nov 2018 |
Publication process dates | |
Accepted | 01 Oct 2018 |
Deposited | 27 Oct 2022 |
Grant ID | U19 CA 148537 |
X01HG007492 | |
HHSN268201200008I | |
NIH NCI U01 CA188392 | |
C5047/A7357 | |
C1287/A10118 | |
C1287/A16563 | |
C5047/A3354 | |
C5047/A10692 | |
C16913/A6135 | |
HEALTH-F2-2009-223175 | |
No. 1 U19 CA 148537-01 |
https://acuresearchbank.acu.edu.au/item/8y641/germline-variation-at-8q24-and-prostate-cancer-risk-in-men-of-european-ancestry
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Publisher's version
OA_Matejcic_2018_Germline_variation_at_8q24_and_prostate.pdf | |
License: CC BY 4.0 | |
File access level: Open |
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