A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer

被引:144
作者
Gudmundsson, Julius [1 ]
Sulem, Patrick [1 ]
Gudbjartsson, Daniel F. [1 ]
Masson, Gisli [1 ]
Agnarsson, Bjarni A. [2 ,3 ]
Benediktsdottir, Kristrun R. [2 ,3 ]
Sigurdsson, Asgeir [1 ]
Magnusson, Olafur Th [1 ]
Gudjonsson, Sigurjon A. [1 ]
Magnusdottir, Droplaug N. [1 ]
Johannsdottir, Hrefna [1 ]
Helgadottir, Hafdis Th [1 ]
Stacey, Simon N. [1 ]
Jonasdottir, Adalbjorg [1 ]
Olafsdottir, Stefania B. [1 ]
Thorleifsson, Gudmar [1 ]
Jonasson, Jon G. [2 ,3 ,4 ]
Tryggvadottir, Laufey [3 ,4 ]
Navarrete, Sebastian [5 ]
Fuertes, Fernando [5 ]
Helfand, Brian T. [6 ]
Hu, Qiaoyan [7 ]
Csiki, Irma E. [8 ]
Mates, Ioan N. [9 ]
Jinga, Viorel [9 ]
Aben, Katja K. H. [10 ,11 ]
van Oort, Inge M. [12 ]
Vermeulen, Sita H. [11 ,13 ]
Donovan, Jenny L. [14 ]
Hamdy, Freddy C. [15 ]
Ng, Chi-Fai [16 ]
Chiu, Peter K. F. [16 ]
Lau, Kin-Mang [17 ]
Ng, Maggie C. Y. [18 ]
Gulcher, Jeffrey R. [1 ]
Kong, Augustine [1 ]
Catalona, William J. [7 ]
Mayordomo, Jose I. [19 ]
Einarsson, Gudmundur V. [20 ]
Barkardottir, Rosa B. [2 ,3 ]
Jonsson, Eirikur [20 ]
Mates, Dana [8 ]
Neal, David E. [21 ]
Kiemeney, Lambertus A. [10 ,11 ,12 ]
Thorsteinsdottir, Unnur [1 ,3 ]
Rafnar, Thorunn [1 ]
Stefansson, Kari [1 ,3 ]
机构
[1] deCODE Genet, Reykjavik, Iceland
[2] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland
[3] Univ Iceland, Fac Med, Reykjavik, Iceland
[4] Iceland Canc Registry, Reykjavik, Iceland
[5] Univ Hosp, Div Radiat Oncol, Zaragoza, Spain
[6] N Shore Univ Hlth Syst, Dept Urol, Glenview, IL USA
[7] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA
[8] Natl Inst Publ Hlth, Bucharest, Romania
[9] Univ Med & Pharm Carol Davila, Bucharest, Romania
[10] Comprehens Canc Ctr Netherlands, Utrecht, Netherlands
[11] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6525 ED Nijmegen, Netherlands
[12] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands
[13] Radboud Univ Nijmegen, Med Ctr, Dept Genet, NL-6525 ED Nijmegen, Netherlands
[14] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England
[15] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg Sci, Oxford OX3 9DU, England
[16] Chinese Univ Hong Kong, Dept Surg, Div Urol, Shatin, Hong Kong, Peoples R China
[17] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China
[18] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China
[19] Univ Zaragoza, Div Med Oncol, Zaragoza, Spain
[20] Landspitali Univ Hosp, Dept Urol, Reykjavik, Iceland
[21] Univ Cambridge, Addenbrookes Hosp, Ctr Oncol, Cambridge CB2 2QQ, England
基金
英国医学研究理事会;
关键词
WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; COLORECTAL-CANCER; COMMON VARIANTS; RISK; SCAN;
D O I
10.1038/ng.2437
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
In Western countries, prostate cancer is the most prevalent cancer of men and one of the leading causes of cancer-related death in men. Several genome-wide association studies have yielded numerous common variants conferring risk of prostate cancer. Here, we analyzed 32.5 million variants discovered by whole-genome sequencing 1,795 Icelanders. We identified a new low-frequency variant at 8q24 associated with prostate cancer in European populations, rs188140481[A] (odds ratio (OR) 2.90; P-combined = 6.2 x 10(-34)), with an average risk allele frequency in controls of 0.54%. This variant is only very weakly correlated (r(2) <= 0.06) with previously reported risk variants at 8q24, and its association remains significant after adjustment for all known risk-associated variants. Carriers of rs188140481[A] were diagnosed with prostate cancer 1.26 years younger than non-carriers (P = 0.0059). We also report results for a previously described HOXB13 variant (rs138213197[T]), confirming it as a prostate cancer risk variant in populations from across Europe.
引用
收藏
页码:1326 / 1329
页数:4
相关论文
共 21 条
[1]   Multiple loci on 8q24 associated with prostate cancer susceptibility [J].
Al Olama, Ali Amin ;
Kote-Jarai, Zsofia ;
Giles, Graham G. ;
Guy, Michelle ;
Morrison, Jonathan ;
Severi, Gianluca ;
Leongamornlert, Daniel A. ;
Tymrakiewicz, Malgorzata ;
Jhavar, Sameer ;
Saunders, Ed ;
Hopper, John L. ;
Southey, Melissa C. ;
Muir, Kenneth R. ;
English, Dallas R. ;
Dearnaley, David P. ;
Ardern-Jones, Audrey T. ;
Hall, Amanda L. ;
O'Brien, Lynne T. ;
Wilkinson, Rosemary A. ;
Sawyer, Emma ;
Lophatananon, Artitaya ;
Horwich, Alan ;
Huddart, Robert A. ;
Khoo, Vincent S. ;
Parker, Christopher C. ;
Woodhouse, Christopher J. ;
Thompson, Alan ;
Christmas, Tim ;
Ogden, Chris ;
Cooper, Colin ;
Donovan, Jenny L. ;
Hamdy, Freddie C. ;
Neal, David E. ;
Eeles, Rosalind A. ;
Easton, Douglas F. .
NATURE GENETICS, 2009, 41 (10) :1058-1060
[2]   A common variant associated with prostate cancer in European and African populations [J].
Amundadottir, Laufey T. ;
Sulem, Patrick ;
Gudmundsson, Julius ;
Helgason, Agnar ;
Baker, Adam ;
Agnarsson, Bjarni A. ;
Sigurdsson, Asgeir ;
Benediktsdottir, Kristrun R. ;
Cazier, Jean-Baptiste ;
Sainz, Jesus ;
Jakobsdottir, Margret ;
Kostic, Jelena ;
Magnusdottir, Droplaug N. ;
Ghosh, Shyamali ;
Agnarsson, Kari ;
Birgisdottir, Birgitta ;
Le Roux, Louise ;
Olafsdottir, Adalheidur ;
Blondal, Thorarinn ;
Andresdottir, Margret ;
Gretarsdottir, Olafia Svandis ;
Bergthorsson, Jon T. ;
Gudbjartsson, Daniel ;
Gylfason, Arnaldur ;
Thorleifsson, Gudmar ;
Manolescu, Andrei ;
Kristjansson, Kristleifur ;
Geirsson, Gudmundur ;
Isaksson, Helgi ;
Douglas, Julie ;
Johansson, Jan-Erik ;
Balter, Katarina ;
Wiklund, Fredrik ;
Montie, James E. ;
Yu, Xiaoying ;
Suarez, Brian K. ;
Ober, Carole ;
Cooney, Kathleen A. ;
Gronberg, Henrik ;
Catalona, William J. ;
Einarsson, Gudmundur V. ;
Barkardottir, Rosa B. ;
Gulcher, Jeffrey R. ;
Kong, Augustine ;
Thorsteinsdottir, Unnur ;
Stefansson, Kari .
NATURE GENETICS, 2006, 38 (06) :652-658
[3]   Cancer as a complex phenotype: Pattern of cancer distribution within and beyond the nuclear family [J].
Amundadottir, LT ;
Thorvaldsson, S ;
Gudbjartsson, DF ;
Sulem, P ;
Kristjansson, K ;
Arnason, S ;
Gulcher, JR ;
Bjornsson, J ;
Kong, A ;
Thorsteinsdottir, U ;
Stefansson, K .
PLOS MEDICINE, 2004, 1 (03) :229-236
[4]   Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk [J].
Crowther-Swanepoel, Dalemari ;
Broderick, Peter ;
Di Bernardo, Maria Chiara ;
Dobbins, Sara E. ;
Torres, Maria ;
Mansouri, Mahmoud ;
Ruiz-Ponte, Clara ;
Enjuanes, Anna ;
Rosenquist, Richard ;
Carracedo, Angel ;
Jurlander, Jesper ;
Campo, Elias ;
Juliusson, Gunnar ;
Montserrat, Emilio ;
Smedby, Karin E. ;
Dyer, Martin J. S. ;
Matutes, Estella ;
Dearden, Claire ;
Sunter, Nicola J. ;
Hall, Andrew G. ;
Mainou-Fowler, Tryfonia ;
Jackson, Graham H. ;
Summerfield, Geoffrey ;
Harris, Robert J. ;
Pettitt, Andrew R. ;
Allsup, David J. ;
Bailey, James R. ;
Pratt, Guy ;
Pepper, Chris ;
Fegan, Chris ;
Parker, Anton ;
Oscier, David ;
Allan, James M. ;
Catovsky, Daniel ;
Houlston, Richard S. .
NATURE GENETICS, 2010, 42 (02) :132-U59
[5]   Genome-wide association study identifies novel breast cancer susceptibility loci [J].
Easton, Douglas F. ;
Pooley, Karen A. ;
Dunning, Alison M. ;
Pharoah, Paul D. P. ;
Thompson, Deborah ;
Ballinger, Dennis G. ;
Struewing, Jeffery P. ;
Morrison, Jonathan ;
Field, Helen ;
Luben, Robert ;
Wareham, Nicholas ;
Ahmed, Shahana ;
Healey, Catherine S. ;
Bowman, Richard ;
Meyer, Kerstin B. ;
Haiman, Christopher A. ;
Kolonel, Laurence K. ;
Henderson, Brian E. ;
Le Marchand, Loic ;
Brennan, Paul ;
Sangrajrang, Suleeporn ;
Gaborieau, Valerie ;
Odefrey, Fabrice ;
Shen, Chen-Yang ;
Wu, Pei-Ei ;
Wang, Hui-Chun ;
Eccles, Diana ;
Evans, D. Gareth ;
Peto, Julian ;
Fletcher, Olivia ;
Johnson, Nichola ;
Seal, Sheila ;
Stratton, Michael R. ;
Rahman, Nazneen ;
Chenevix-Trench, Georgia ;
Bojesen, Stig E. ;
Nordestgaard, Borge G. ;
Axelsson, Christen K. ;
Garcia-Closas, Montserrat ;
Brinton, Louise ;
Chanock, Stephen ;
Lissowska, Jolanta ;
Peplonska, Beata ;
Nevanlinna, Heli ;
Fagerholm, Rainer ;
Eerola, Hannaleena ;
Kang, Daehee ;
Yoo, Keun-Young ;
Noh, Dong-Young ;
Ahn, Sei-Hyun .
NATURE, 2007, 447 (7148) :1087-U7
[6]   Germline Mutations in HOXB13 and Prostate-Cancer Risk [J].
Ewing, Charles M. ;
Ray, Anna M. ;
Lange, Ethan M. ;
Zuhlke, Kimberly A. ;
Robbins, Christiane M. ;
Tembe, Waibhav D. ;
Wiley, Kathleen E. ;
Isaacs, Sarah D. ;
Johng, Dorhyun ;
Wang, Yunfei ;
Bizon, Chris ;
Yan, Guifang ;
Gielzak, Marta ;
Partin, Alan W. ;
Shanmugam, Vijayalakshmi ;
Izatt, Tyler ;
Sinari, Shripad ;
Craig, David W. ;
Zheng, S. Lilly ;
Walsh, Patrick C. ;
Montie, James E. ;
Xu, Jianfeng ;
Carpten, John D. ;
Isaacs, William B. ;
Cooney, Kathleen A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (02) :141-149
[7]   Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes [J].
Gudmundsson, Julius ;
Sulem, Patrick ;
Steinthorsdottir, Valgerdur ;
Bergthorsson, Jon T. ;
Thorleifsson, Gudmar ;
Manolescu, Andrei ;
Rafnar, Thorunn ;
Gudbjartsson, Daniel ;
Agnarsson, Bjarni A. ;
Baker, Adam ;
Sigurdsson, Asgeir ;
Benediktsdottir, Kristrun R. ;
Jakobsdottir, Margret ;
Blondal, Thorarinn ;
Stacey, Simon N. ;
Helgason, Agnar ;
Gunnarsdottir, Steinunn ;
Olafsdottir, Adalheidur ;
Kristinsson, Kari T. ;
Birgisdottir, Birgitta ;
Ghosh, Shyamali ;
Thorlacius, Steinunn ;
Magnusdottir, Dana ;
Stefansdottir, Gerdur ;
Kristjansson, Kristleifur ;
Bagger, Yu ;
Wilensky, Robert L. ;
Reilly, Muredach P. ;
Morris, Andrew D. ;
Kimber, Charlotte H. ;
Adeyemo, Adebowale ;
Chen, Yuanxiu ;
Zhou, Jie ;
So, Wing-Yee ;
Tong, Peter C. Y. ;
Ng, Maggie C. Y. ;
Hansen, Torben ;
Andersen, Gitte ;
Borch-Johnsen, Knut ;
Jorgensen, Torben ;
Tres, Alejandro ;
Fuertes, Fernando ;
Ruiz-Echarri, Manuel ;
Asin, Laura ;
Saez, Berta ;
van Boven, Erica ;
Klaver, Siem ;
Swinkels, Dorine W. ;
Aben, Katja K. ;
Graif, Theresa .
NATURE GENETICS, 2007, 39 (08) :977-983
[8]   Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24 [J].
Gudmundsson, Julius ;
Sulem, Patrick ;
Manolescu, Andrei ;
Amundadottir, Laufey T. ;
Gudbjartsson, Daniel ;
Helgason, Agnar ;
Rafnar, Thorunn ;
Bergthorsson, Jon T. ;
Agnarsson, Bjarni A. ;
Baker, Adam ;
Sigurdsson, Asgeir ;
Benediktsdottir, Kristrun R. ;
Jakobsdottir, Margret ;
Xu, Jianfeng ;
Blondal, Thorarinn ;
Kostic, Jelena ;
Sun, Jielin ;
Ghosh, Shyamali ;
Stacey, Simon N. ;
Mouy, Magali ;
Saemundsdottir, Jona ;
Backman, Valgerdur M. ;
Kristjansson, Kristleifur ;
Tres, Alejandro ;
Partin, Alan W. ;
Albers-Akkers, Marjo T. ;
Marcos, Javier Godino-Ivan ;
Walsh, Patrick C. ;
Swinkels, Dorine W. ;
Navarrete, Sebastian ;
Isaacs, Sarah D. ;
Aben, Katja K. ;
Graif, Theresa ;
Cashy, John ;
Ruiz-Echarri, Manuel ;
Wiley, Kathleen E. ;
Suarez, Brian K. ;
Witjes, J. Alfred ;
Frigge, Mike ;
Ober, Carole ;
Jonsson, Eirikur ;
Einarsson, Gudmundur V. ;
Mayordomo, Jose I. ;
Kiemeney, Lambertus A. ;
Isaacs, William B. ;
Catalona, William J. ;
Barkardottir, Rosa B. ;
Gulcher, Jeffrey R. ;
Thorsteinsdottir, Unnur ;
Kong, Augustine .
NATURE GENETICS, 2007, 39 (05) :631-637
[9]   Discovery of common variants associated with low TSH levels and thyroid cancer risk [J].
Gudmundsson, Julius ;
Sulem, Patrick ;
Gudbjartsson, Daniel F. ;
Jonasson, Jon G. ;
Masson, Gisli ;
He, Huiling ;
Jonasdottir, Aslaug ;
Sigurdsson, Asgeir ;
Stacey, Simon N. ;
Johannsdottir, Hrefna ;
Helgadottir, Hafdis Th ;
Li, Wei ;
Nagy, Rebecca ;
Ringel, Matthew D. ;
Kloos, Richard T. ;
de Visser, Marieke C. H. ;
Plantinga, Theo S. ;
den Heijer, Martin ;
Aguillo, Esperanza ;
Panadero, Angeles ;
Prats, Enrique ;
Garcia-Castano, Almudena ;
De Juan, Ana ;
Rivera, Fernando ;
Walters, G. Bragi ;
Bjarnason, Hjordis ;
Tryggvadottir, Laufey ;
Eyjolfsson, Gudmundur I. ;
Bjornsdottir, Unnur S. ;
Holm, Hilma ;
Olafsson, Isleifur ;
Kristjansson, Kristleifur ;
Kristvinsson, Hoskuldur ;
Magnusson, Olafur T. ;
Thorleifsson, Gudmar ;
Gulcher, Jeffrey R. ;
Kong, Augustine ;
Kiemeney, Lambertus A. L. M. ;
Jonsson, Thorvaldur ;
Hjartarson, Hannes ;
Mayordomo, Jose I. ;
Netea-Maier, Romana T. ;
de la Chapelle, Albert ;
Hrafnkelsson, Jon ;
Thorsteinsdottir, Unnur ;
Rafnar, Thorunn ;
Stefansson, Kari .
NATURE GENETICS, 2012, 44 (03) :319-U126
[10]   Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility [J].
Gudmundsson, Julius ;
Sulem, Patrick ;
Gudbjartsson, Daniel F. ;
Blondal, Thorarinn ;
Gylfason, Arnaldur ;
Agnarsson, Bjarni A. ;
Benediktsdottir, Kristrun R. ;
Magnusdottir, Droplaug N. ;
Orlygsdottir, Gudbjorg ;
Jakobsdottir, Margret ;
Stacey, Simon N. ;
Sigurdsson, Asgeir ;
Wahlfors, Tiina ;
Tammela, Teuvo ;
Breyer, Joan P. ;
McReynolds, Kate M. ;
Bradley, Kevin M. ;
Saez, Berta ;
Godino, Javier ;
Navarrete, Sebastian ;
Fuertes, Fernando ;
Murillo, Laura ;
Polo, Eduardo ;
Aben, Katja K. ;
van Oort, Inge M. ;
Suarez, Brian K. ;
Helfand, Brian T. ;
Kan, Donghui ;
Zanon, Carlo ;
Frigge, Michael L. ;
Kristjansson, Kristleifur ;
Gulcher, Jeffrey R. ;
Einarsson, Gudmundur V. ;
Jonsson, Eirikur ;
Catalona, William J. ;
Mayordomo, Jose I. ;
Kiemeney, Lambertus A. ;
Smith, Jeffrey R. ;
Schleutker, Johanna ;
Barkardottir, Rosa B. ;
Kong, Augustine ;
Thorsteinsdottir, Unnur ;
Rafnar, Thorunn ;
Stefansson, Kari .
NATURE GENETICS, 2009, 41 (10) :1122-U104