A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

被引：358

作者：

Al Olama, Ali Amin ^{[1
]}

Kote-Jarai, Zsofia ^{[2
]}

Berndt, Sonja I. ^{[3
]}

Conti, David V. ^{[4
,5
]}

Schumacher, Fredrick ^{[4
,5
]}

Han, Ying ^{[4
]}

Benlloch, Sara ^{[1
]}

Hazelett, Dennis J. ^{[4
,5
]}

Wang, Zhaoming ^{[3
,6
]}

Saunders, Ed ^{[2
]}

Leongamornlert, Daniel ^{[2
]}

Lindstrom, Sara ^{[7
]}

Jugurnauth-Little, Sara ^{[2
]}

Dadaev, Tokhir ^{[2
]}

Tymrakiewicz, Malgorzata ^{[2
]}

Stram, Daniel O. ^{[4
,5
]}

Rand, Kristin ^{[4
]}

Wan, Peggy ^{[4
]}

Stram, Alex ^{[4
]}

Sheng, Xin ^{[4
]}

Pooler, Loreall C. ^{[4
]}

Park, Karen ^{[4
]}

Xia, Lucy ^{[4
]}

Tyrer, Jonathan ^{[1
]}

Kolonel, Laurence N. ^{[8
]}

Le Marchand, Loic ^{[8
]}

Hoover, Robert N. ^{[3
]}

Machiela, Mitchell J. ^{[3
]}

Yeager, Merideth ^{[3
]}

Burdette, Laurie ^{[3
]}

Chung, Charles C. ^{[3
]}

Hutchinson, Amy ^{[3
]}

Yu, Kai ^{[3
]}

Goh, Chee ^{[2
]}

Ahmed, Mahbubl ^{[2
]}

Govindasami, Koveela ^{[2
]}

Guy, Michelle ^{[2
]}

Tammela, Teuvo L. J. ^{[9
,10
]}

Auvinen, Anssi ^{[11
]}

Wahlfors, Tlina ^{[12
,13
]}

Schleutker, Johanna ^{[12
,13
,14
]}

Visakorpi, Tapio ^{[15
,16
]}

Leinonen, Katri A. ^{[15
,16
]}

Xu, Jianfeng ^{[17
]}

Aly, Markus ^{[18
,19
]}

Donovan, Jenny ^{[20
]}

Travis, Ruth C. ^{[21
]}

Key, Tim J. ^{[21
]}

Siddiq, Afshan ^{[22
]}

Canzian, Federico ^{[23
]}

机构：

[1] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England

[2] Inst Canc Res, London SW3 6JB, England

[3] Natl Canc Inst, US NIH, Div Canc Epidemiol & Genet, Bethesda, MD USA

[4] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[5] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA

[6] SAIC Frederick Inc, Natl Canc Inst, Div Canc Epidemiol & Genet, Canc Genom Res Lab, Frederick, MD USA

[7] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA

[8] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA

[9] Univ Tampere, Tampere Univ Hosp, Dept Urol, FIN-33101 Tampere, Finland

[10] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland

[11] Univ Tampere, Sch Hlth Sci, Dept Epidemiol, FIN-33101 Tampere, Finland

[12] Univ Tampere, BioMediTech, Tampere, Finland

[13] Univ Tampere, FimLab Labs, Tampere, Finland

[14] Univ Turku, Inst Biomed, Dept Biochem Med, Turku, Finland

[15] Univ Tampere, BioMediTech, Inst Biomed Technol, Tampere, Finland

[16] Tampere Univ Hosp, Tampere, Finland

[17] Wake Forest Sch Med, Ctr Canc Genom, Winston Salem, NC USA

[18] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[19] Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden

[20] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

[21] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England

[22] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England

[23] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany

[24] Univ Cambridge, Clin Gerontol Unit, Cambridge, England

[25] RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[26] RIKEN, Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[27] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England

[28] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark

[29] Univ Copenhagen, Fac Hlth & Med Sci, Herlev, Denmark

[30] Copenhagen Univ Hosp, Herlev Hosp, Dept Urol, Herlev, Denmark

[31] Copenhagen Univ Hosp, Rigshosp, Copenhagen Prostate Canc Ctr, Dept Urol, Copenhagen, Denmark

[32] Mayo Clin, Rochester, MN USA

[33] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[34] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA

[35] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[36] Cedars Sinai, Translat Pathol, Los Angeles, CA USA

[37] Prostate Ctr, Vancouver, BC, Canada

[38] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[39] Univ Hosp Ulm, Dept Urol, Ulm, Germany

[40] Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-80290 Munich, Germany

[41] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[42] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA

[43] Univ Ghana, Sch Med, Accra, Ghana

[44] Korle Bu Teaching Hosp, Accra, Ghana

[45] Westat Corp, Rockville, MD USA

[46] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA

[47] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA

[48] Vet Affairs Med Ctr, George E Wahlen Dept, Salt Lake City, UT 84148 USA

[49] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland

[50] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA

来源：

NATURE GENETICS | 2014年 / 46卷 / 10期

基金：

英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; COMMON VARIANTS; MYOSIN VI; RISK; JAPANESE; GLIOMA; 22Q13; MEN;

D O I：

10.1038/ng.3094

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 x 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

引用

页码：1103 / 1109

页数：7

共 29 条

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Yeboah, Edward D. ;

Tettey, Yao ;

Biritwum, Richard B. ;

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Truelove, Ann ;

Niwa, Shelley ;

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Chokkalingam, Annand P. ;

Chu, Lisa W. ;

Yeager, Meredith ;

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Isaacs, Sarah D. ;

Cheng, Yu ;

Li, Ge ;

Sun, Jielin ;

Chang, Bao-Li ;

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Wiley, Kathleen E. ;

Balter, Katarina ;

Stattin, Par ;

Adami, Hans-Olov ;

Gielzak, Marta ;

Yan, Guifang ;

Sauvageot, Jurga ;

Liu, Wennuan ;

Kim, Jin Woo ;

Bleecker, Eugene R. ;

Meyers, Deborah A. ;

Trock, Bruce J. ;

Partin, Alan W. ;

Walsh, Patrick C. ;

Isaacs, William B. ;

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Xu, Jianfeng ;

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Jugurnauth, Sarah K. ;

Mulholland, Shani ;

Leongamornlert, Daniel A. ;

Edwards, Stephen M. ;

Morrison, Jonathan ;

Field, Helen I. ;

Southey, Melissa C. ;

Severi, Gianluca ;

Donovan, Jenny L. ;

Hamdy, Freddie C. ;

Dearnaley, David P. ;

Muir, Kenneth R. ;

Smith, Charmaine ;

Bagnato, Melisa ;

Ardern-Jones, Audrey T. ;

Hall, Amanda L. ;

O'Brien, Lynne T. ;

Gehr-Swain, Beatrice N. ;

Wilkinson, Rosemary A. ;

Cox, Angie ;

Lewis, Sarah ;

Brown, Paul M. ;

Jhavar, Sameer G. ;

Tymrakiewicz, Malgorzata ;

Lophatananon, Artitaya ;

Bryant, Sarah L. ;

Horwich, Alan ;

Huddart, Robert A. ;

Khoo, Vincent S. ;

Parker, Christopher C. ;

Woodhouse, Christopher J. ;

Thompson, Alan ;

Christmas, Tim ;

Ogden, Chris ;

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Al Olama, Ali Amin ;

Benlloch, Sara ;

Saunders, Edward J. ;

Leongamornlert, Daniel A. ;

Tymrakiewicz, Malgorzata ;

Ghoussaini, Maya ;

Luccarini, Craig ;

Dennis, Joe ;

Jugurnauth-Little, Sarah ;

Dadaev, Tokhir ;

Neal, David E. ;

Hamdy, Freddie C. ;

Donovan, Jenny L. ;

Muir, Ken ;

Giles, Graham G. ;

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Wiklund, Fredrik ;

Gronberg, Henrik ;

Haiman, Christopher A. ;

Schumacher, Fredrick ;

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Lindstrom, Sara ;

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Hunter, David J. ;

Gapstur, Susan ;

Chanock, Stephen J. ;

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Albanes, Demetrius ;

Andriole, Gerald ;

Schleutker, Johanna ;

Weischer, Maren ;

Canzian, Federico ;

Riboli, Elio ;

Key, Tim J. ;

Travis, Ruth C. ;

Campa, Daniele ;

Ingles, Sue A. ;

John, Esther M. ;

Hayes, Richard B. ;

Pharoah, Paul D. P. ;

Pashayan, Nora ;

Khaw, Kay-Tee ;

Stanford, Janet L. ;

Ostrander, Elaine A. ;

Signorello, Lisa B. ;

Thibodeau, Stephen N. ;

Schaid, Dan ;

Maier, Christiane .

NATURE GENETICS, 2013, 45 (04) :385-391

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Bataille, Veronique ;

Hayward, Nicholas K. ;

Duffy, David L. ;

Bishop, Julia A. Newton ;

Pastinen, Tomi ;

Cervino, Alessandra ;

Zhao, Zhen Z. ;

Deloukas, Panos ;

Soranzo, Nicole ;

Elder, David E. ;

Barrett, Jennifer H. ;

Martin, Nicholas G. ;

Bishop, D. Timothy ;

Montgomery, Grant W. ;

Spector, Timothy D. .

NATURE GENETICS, 2009, 41 (08) :915-U76

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Gudmundsson, Julius ;

Sulem, Patrick ;

Gudbjartsson, Daniel F. ;

Blondal, Thorarinn ;

Gylfason, Arnaldur ;

Agnarsson, Bjarni A. ;

Benediktsdottir, Kristrun R. ;

Magnusdottir, Droplaug N. ;

Orlygsdottir, Gudbjorg ;

Jakobsdottir, Margret ;

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Haiman, Christopher A. ;

Chen, Gary K. ;

Blot, William J. ;

Strom, Sara S. ;

Berndt, Sonja I. ;

Kittles, Rick A. ;

Rybicki, Benjamin A. ;

Isaacs, William B. ;

Ingles, Sue A. ;

Stanford, Janet L. ;

Diver, W. Ryan ;

Witte, John S. ;

Chanock, Stephen J. ;

Kolb, Suzanne ;

Signorello, Lisa B. ;

Yamamura, Yuko ;

Neslund-Dudas, Christine ;

Thun, Michael J. ;

Murphy, Adam ;

Casey, Graham ;

Sheng, Xin ;

Wan, Peggy ;

Pooler, Loreall C. ;

Monroe, Kristine R. ;

Waters, Kevin M. ;

Le Marchand, Loic ;

Kolonel, Laurence N. ;

Stram, Daniel O. ;

Henderson, Brian E. .

PLOS GENETICS, 2011, 7 (05)

← 1 2 3 →

共 29 条

[1] Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese [J].

Akamatsu, Shusuke ;

Takata, Ryo ;

Haiman, Christopher A. ;

Takahashi, Atsushi ;

Inoue, Takahiro ;

Kubo, Michiaki ;

Furihata, Mutsuo ;

Kamatani, Naoyuki ;

Inazawa, Johji ;

Chen, Gary K. ;

Le Marchand, Loic ;

Kolonel, Laurence N. ;

Katoh, Takahiko ;

Yamano, Yuko ;

Yamakado, Minoru ;

Takahashi, Hiroyuki ;

Yamada, Hiroki ;

Egawa, Shin ;

Fujioka, Tomoaki ;

Henderson, Brian E. ;

Habuchi, Tomonori ;

Ogawa, Osamu ;

Nakamura, Yusuke ;

Nakagawa, Hidewaki .

NATURE GENETICS, 2012, 44 (04) :426-U234

[2] Evaluating Genetic Risk for Prostate Cancer among Japanese and Latinos [J].

Cheng, Iona ;

Chen, Gary K. ;

Nakagawa, Hidewaki ;

He, Jing ;

Wan, Peggy ;

Laurie, Cathy C. ;

Shen, Jess ;

Sheng, Xin ;

Pooler, Loreall C. ;

Crenshaw, Andrew T. ;

Mirel, Daniel B. ;

Takahashi, Atsushi ;

Kubo, Michiaki ;

Nakamura, Yusuke ;

Al Olama, Ali Amin ;

Benlloch, Sara ;

Donovan, Jenny L. ;

Guy, Michelle ;

Hamdy, Freddie C. ;

Kote-Jarai, Zsofia ;

Neal, David E. ;

Wilkens, Lynne R. ;

Monroe, Kristine R. ;

Stram, Daniel O. ;

Muir, Kenneth ;

Eeles, Rosalind A. ;

Easton, Douglas F. ;

Kolonel, Laurence N. ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Haiman, Christopher A. .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2012, 21 (11) :2048-2058

[3] A genome-wide association study of prostate cancer in West African men [J].

Cook, Michael Blaise ;

Wang, Zhaoming ;

Yeboah, Edward D. ;

Tettey, Yao ;

Biritwum, Richard B. ;

Adjei, Andrew A. ;

Tay, Evelyn ;

Truelove, Ann ;

Niwa, Shelley ;

Chung, Charles C. ;

Chokkalingam, Annand P. ;

Chu, Lisa W. ;

Yeager, Meredith ;

Hutchinson, Amy ;

Yu, Kai ;

Rand, Kristin A. ;

Haiman, Christopher A. ;

Hoover, Robert N. ;

Hsing, Ann W. ;

Chanock, Stephen J. .

HUMAN GENETICS, 2014, 133 (05) :509-521

[4] Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB21P [J].

Duggan, David ;

Zheng, Siqun L. ;

Knowlton, Michele ;

Benitez, Debbie ;

Dimitrov, Latchezar ;

Wiklund, Fredrik ;

Robbins, Christiane ;

Isaacs, Sarah D. ;

Cheng, Yu ;

Li, Ge ;

Sun, Jielin ;

Chang, Bao-Li ;

Marovich, Leslie ;

Wiley, Kathleen E. ;

Balter, Katarina ;

Stattin, Par ;

Adami, Hans-Olov ;

Gielzak, Marta ;

Yan, Guifang ;

Sauvageot, Jurga ;

Liu, Wennuan ;

Kim, Jin Woo ;

Bleecker, Eugene R. ;

Meyers, Deborah A. ;

Trock, Bruce J. ;

Partin, Alan W. ;

Walsh, Patrick C. ;

Isaacs, William B. ;

Gronberg, Henrik ;

Xu, Jianfeng ;

Carpten, John D. .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2007, 99 (24) :1836-1844

[5] The genetic epidemiology of prostate cancer and its clinical implications [J].

Eeles, Rosalind ;

Goh, Chee ;

Castro, Elena ;

Bancroft, Elizabeth ;

Guy, Michelle ;

Al Olama, Ali Amin ;

Easton, Douglas ;

Kote-Jarai, Zsofia .

NATURE REVIEWS UROLOGY, 2014, 11 (01) :18-31

[6] Multiple newly identified loci associated with prostate cancer susceptibility [J].

Eeles, Rosalind A. ;

Kote-Jarai, Zsofia ;

Giles, Graham G. ;

Al Olama, Ali Amin ;

Guy, Michelle ;

Jugurnauth, Sarah K. ;

Mulholland, Shani ;

Leongamornlert, Daniel A. ;

Edwards, Stephen M. ;

Morrison, Jonathan ;

Field, Helen I. ;

Southey, Melissa C. ;

Severi, Gianluca ;

Donovan, Jenny L. ;

Hamdy, Freddie C. ;

Dearnaley, David P. ;

Muir, Kenneth R. ;

Smith, Charmaine ;

Bagnato, Melisa ;

Ardern-Jones, Audrey T. ;

Hall, Amanda L. ;

O'Brien, Lynne T. ;

Gehr-Swain, Beatrice N. ;

Wilkinson, Rosemary A. ;

Cox, Angie ;

Lewis, Sarah ;

Brown, Paul M. ;

Jhavar, Sameer G. ;

Tymrakiewicz, Malgorzata ;

Lophatananon, Artitaya ;

Bryant, Sarah L. ;

Horwich, Alan ;

Huddart, Robert A. ;

Khoo, Vincent S. ;

Parker, Christopher C. ;

Woodhouse, Christopher J. ;

Thompson, Alan ;

Christmas, Tim ;

Ogden, Chris ;

Fisher, Cyril ;

Jamieson, Charles ;

Cooper, Colin S. ;

English, Dallas R. ;

Hopper, John L. ;

Neal, David E. ;

Easton, Douglas F. .

NATURE GENETICS, 2008, 40 (03) :316-321

[7] Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array [J].

Eeles, Rosalind A. ;

Al Olama, Ali Amin ;

Benlloch, Sara ;

Saunders, Edward J. ;

Leongamornlert, Daniel A. ;

Tymrakiewicz, Malgorzata ;

Ghoussaini, Maya ;

Luccarini, Craig ;

Dennis, Joe ;

Jugurnauth-Little, Sarah ;

Dadaev, Tokhir ;

Neal, David E. ;

Hamdy, Freddie C. ;

Donovan, Jenny L. ;

Muir, Ken ;

Giles, Graham G. ;

Severi, Gianluca ;

Wiklund, Fredrik ;

Gronberg, Henrik ;

Haiman, Christopher A. ;

Schumacher, Fredrick ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Lindstrom, Sara ;

Kraft, Peter ;

Hunter, David J. ;

Gapstur, Susan ;

Chanock, Stephen J. ;

Berndt, Sonja I. ;

Albanes, Demetrius ;

Andriole, Gerald ;

Schleutker, Johanna ;

Weischer, Maren ;

Canzian, Federico ;

Riboli, Elio ;

Key, Tim J. ;

Travis, Ruth C. ;

Campa, Daniele ;

Ingles, Sue A. ;

John, Esther M. ;

Hayes, Richard B. ;

Pharoah, Paul D. P. ;

Pashayan, Nora ;

Khaw, Kay-Tee ;

Stanford, Janet L. ;

Ostrander, Elaine A. ;

Signorello, Lisa B. ;

Thibodeau, Stephen N. ;

Schaid, Dan ;

Maier, Christiane .

NATURE GENETICS, 2013, 45 (04) :385-391

[8] Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi [J].

Falchi, Mario ;

Bataille, Veronique ;

Hayward, Nicholas K. ;

Duffy, David L. ;

Bishop, Julia A. Newton ;

Pastinen, Tomi ;

Cervino, Alessandra ;

Zhao, Zhen Z. ;

Deloukas, Panos ;

Soranzo, Nicole ;

Elder, David E. ;

Barrett, Jennifer H. ;

Martin, Nicholas G. ;

Bishop, D. Timothy ;

Montgomery, Grant W. ;

Spector, Timothy D. .

NATURE GENETICS, 2009, 41 (08) :915-U76

[9] 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 ;

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