Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

被引：302

作者：

Conti, David, V ^{[1
]}

Darst, Burcu F. ^{[1
]}

Moss, Lilit C. ^{[1
]}

Saunders, Edward J. ^{[2
]}

Sheng, Xin ^{[1
]}

Chou, Alisha ^{[1
]}

Schumacher, Fredrick R. ^{[3
,4
]}

Al Olama, Ali Amin ^{[5
,6
]}

Benlloch, Sara ^{[5
]}

Dadaev, Tokhir ^{[2
]}

Brook, Mark N. ^{[2
]}

Sahimi, Ali ^{[1
]}

Hoffmann, Thomas J. ^{[7
,8
]}

Takahashi, Atushi ^{[9
,10
]}

Matsuda, Koichi ^{[11
,12
]}

Momozawa, Yukihide ^{[13
]}

Fujita, Masashi ^{[14
]}

Muir, Kenneth ^{[15
,16
]}

Lophatananon, Artitaya ^{[15
]}

Wan, Peggy ^{[1
]}

Le Marchand, Loic ^{[17
]}

Wilkens, Lynne R. ^{[17
]}

Stevens, Victoria L. ^{[18
]}

Gapstur, Susan M. ^{[18
]}

Carter, Brian D. ^{[18
]}

Schleutker, Johanna ^{[19
,20
]}

Tammela, Teuvo L. J. ^{[21
,22
]}

Sipeky, Csilla ^{[19
]}

Auvinen, Anssi ^{[23
]}

Giles, Graham G. ^{[24
,25
,26
]}

Southey, Melissa C. ^{[26
]}

MacInnis, Robert J. ^{[24
,25
]}

Cybulski, Cezary ^{[27
]}

Wokolorczyk, Dominika ^{[27
]}

Lubinski, Jan ^{[27
]}

Neal, David E. ^{[28
,29
,30
]}

Donovan, Jenny L. ^{[31
]}

Hamdy, Freddie C. ^{[32
,33
]}

Martin, Richard M. ^{[31
,34
,35
]}

Nordestgaard, Borge G. ^{[36
,37
]}

Nielsen, Sune F. ^{[36
,37
]}

Weischer, Maren ^{[37
]}

Bojesen, Stig E. ^{[36
,37
]}

Roder, Martin Andreas ^{[38
]}

Iversen, Peter ^{[38
]}

Batra, Jyotsna ^{[39
,40
,41
]}

Chambers, Suzanne ^{[42
]}

Moya, Leire ^{[39
,40
,41
]}

Horvath, Lisa ^{[43
,44
]}

Clements, Judith A. ^{[39
,40
,41
]}

机构：

[1] Univ Southern Calif, Ctr Genet Epidemiol, Keck Sch Med, Dept Prevent Med,Norris Comprehens Canc Ctr, Los Angeles, CA 90007 USA

[2] Inst Canc Res, London, England

[3] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA

[4] Univ Hosp, Seidman Canc Ctr, Cleveland, OH USA

[5] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England

[6] Univ Cambridge, Dept Clin Neurosci, Stroke Res Grp, Cambridge, England

[7] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[8] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

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

[10] Natl Cerebral & Cardiovasc Ctr Res Inst, Dept Genom Med, Suita, Osaka, Japan

[11] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Lab Clin Genome Sequencing, Tokyo, Japan

[12] Biobank, Tokyo, Japan

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

[14] RIKEN, Lab Canc Genom, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[15] Univ Manchester, Fac Biol Med & Hlth, Sch Hlth Sci, Hlth Serv Res & Primary Care,Div Populat Hlth, Manchester, Lancs, England

[16] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England

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

[18] Amer Canc Soc, Res Program, Behav & Epidemiol Res Grp, Atlanta, GA 30329 USA

[19] Univ Turku, Inst Biomed, Turku, Finland

[20] Turku Univ Hosp, Dept Med Genet, Lab Div, Genom, Turku, Finland

[21] Tampere Univ, Tampere Univ Hosp, Tampere, Finland

[22] Tampere Univ, Fac Med & Hlth Technol, Tampere, Finland

[23] Tampere Univ, Fac Social Sci, Unit Hlth Sci, Tampere, Finland

[24] Canc Council Victoria, Canc Epidemiol Div, Melbourne, Vic, Australia

[25] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia

[26] Monash Univ, Sch Clin Sci, Precis Med, Monash Hlth, Clayton, Vic, Australia

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

[28] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg Sci, Oxford, England

[29] Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Cambridge, England

[30] Li Ka Shing Ctr, Cambridge Res Inst, Canc Res UK, Cambridge, England

[31] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England

[32] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England

[33] Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford, England

[34] Univ Bristol, Natl Inst Hlth Res NIHR Biomed Res Ctr, Bristol, Avon, England

[35] Univ Bristol, Med Res Council MRC Integrat Epidemiol Unit, Bristol, Avon, England

[36] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark

[37] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Copenhagen, Denmark

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

[39] Queensland Univ Technol, Australian Prostate Canc Res Ctr Queensland, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia

[40] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia

[41] Translat Res Inst, Brisbane, Qld, Australia

[42] Univ Technol, Sydney, NSW, Australia

[43] Chris OBrien Lifehouse COBLH, Sydney, NSW, Australia

[44] Garvan Inst Med Res, Sydney, NSW, Australia

[45] Univ Adelaide, Adelaide Med Sch, Dame Roma Mitchell Canc Res Labs, Adelaide, SA, Australia

[46] Monash Univ, Biomed Discovery Inst, Dept Anat & Dev Biol, Melbourne, Vic, Australia

[47] Peter MacCallum Canc Ctr, Canc Res Div, Prostate Canc Translat Res Program, Melbourne, Vic, Australia

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

[49] Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[50] Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden

来源：

NATURE GENETICS | 2021年 / 53卷 / 01期

基金：

美国国家卫生研究院;

关键词：

BREAST-CANCER; ODDS RATIOS; VARIANTS; IMPUTATION; MUTATIONS; SEQUENCE; BRCA2; 8Q24;

D O I：

10.1038/s41588-020-00748-0

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

引用

页码：11 / 15

页数：5

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