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

Conti, D. V.; Darst, B. F.; Moss, L. C.; Saunders, E. J.; Sheng, X.; Chou, A.; Schumacher, F. R.; Olama, A. A. A.; Benlloch, S.; Dadaev, T.; Brook, M. N.; Sahimi, A.; Hoffmann, T. J.; Takahashi, A.; Matsuda, K.; Momozawa, Y.; Fujita, M.; Muir, K.; Lophatananon, A.; Wan, P.; Le Marchand, L.; Wilkens, L. R.; Stevens, V. L.; Gapstur, S. M.; Carter, B. D.; Schleutker, J.; Tammela, T. L. J.; Sipeky, C.; Auvinen, A.; Giles, G. G.; Southey, M. C.; MacInnis, R. J.; Cybulski, C.; Wokołorczyk, D.; Lubiński, J.; Neal, D. E.; Donovan, J. L.; Hamdy, F. C.; Martin, R. M.; Nordestgaard, B. G.; Nielsen, S. F.; Weischer, M.; Bojesen, S. E.; Røder, M. A.; Iversen, P.; Batra, J.; Chambers, S.; Moya, L.; Horvath, L.; Clements, J. A.; Tilley, W.; Risbridger, G. P.; Gronberg, H.; Aly, M.; Szulkin, R.; Eklund, M.; Nordström, T.; Pashayan, N.; Dunning, A. M.; Ghoussaini, M.; Travis, R. C.; Key, T. J.; Riboli, E.; Park, J. Y.; Sellers, T. A.; Lin, H. Y.; Albanes, D.; Weinstein, S. J.; Mucci, L. A.; Giovannucci, E.; Lindstrom, S.; Kraft, P.; Hunter, D. J.; Penney, K. L.; Turman, C.; Tangen, C. M.; Goodman, P. J.; Thompson, I. M., Jr.; Hamilton, R. J.; Fleshner, N. E.; Finelli, A.; Parent, M.; Stanford, J. L.; Ostrander, E. A.; Geybels, M. S.; Koutros, S.; Freeman, L. E. B.; Stampfer, M.; Wolk, A.; Håkansson, N.; Andriole, G. L.; Hoover, R. N.; Machiela, M. J.; Sørensen, K. D.; Borre, M.; Blot, W. J.; Zheng, W.; Yeboah, E. D.; Mensah, J. E.; Lu, Y. J.; Zhang, H. W.; Feng, N.; Mao, X.; Wu, Y.; Zhao, S. C.; Sun, Z.; Thibodeau, S. N.; McDonnell, S. K.; Schaid, D. J.; West, Catharine M L; Burnet, Neil G; Barnett, G.; Maier, C.; Schnoeller, T.; Luedeke, M.; Kibel, A. S.; Drake, B. F.; Cussenot, O.; Cancel-Tassin, G.; Menegaux, F.; Truong, T.; Koudou, Y. A.; John, E. M.; Grindedal, E. M.; Maehle, L.; Khaw, K. T.; Ingles, S. A.; Stern, M. C.; Vega, A.; Gómez-Caamaño, A.; Fachal, L.; Rosenstein, B. S.; Kerns, S. L.; Ostrer, H.; Teixeira, M. R.; Paulo, P.; Brandão, A.; Watya, S.; Lubwama, A.; Bensen, J. T.; Fontham, E. T. H.; Mohler, J.; Taylor, J. A.; Kogevinas, M.; Llorca, J.; Castaño-Vinyals, G.; Cannon-Albright, L.; Teerlink, C. C.; Huff, C. D.; Strom, S. S.; Multigner, L.; Blanchet, P.; Brureau, L.; Kaneva, R.; Slavov, C.; Mitev, V.; Leach, R. J.; Weaver, B.; Brenner, H.; Cuk, K.; Holleczek, B.; Saum, K. U.; Klein, E. A.; Hsing, A. W.; Kittles, R. A.; Murphy, A. B.; Logothetis, C. J.; Kim, J.; Neuhausen, S. L.; Steele, L.; Ding, Y. C.; Isaacs, W. B.; Nemesure, B.; Hennis, A. J. M.; Carpten, J.; Pandha, H.; Michael, A.; De Ruyck, K.; De Meerleer, G.; Ost, P.; Xu, J.; Razack, A.; Lim, J.; Teo, S. H.; Newcomb, L. F.; Lin, D. W.; Fowke, J. H.; Neslund-Dudas, C.; Rybicki, B. A.; Gamulin, M.; Lessel, D.; Kulis, T.; Usmani, N.; Singhal, S.; Parliament, M.; Claessens, F.; Joniau, S.; Van den Broeck, T.; Gago-Dominguez, M.; Castelao, J. E.; Martinez, M. E.; Larkin, S.; Townsend, Paul A; Aukim-Hastie, C.; Bush, W. S.; Aldrich, M. C.; Crawford, D. C.; Srivastava, S.; Cullen, J. C.; Petrovics, G.; Casey, G.; Roobol, M. J.; Jenster, G.; van Schaik, R. H. N.; Hu, J. J.; Sanderson, M.; Varma, R.; McKean-Cowdin, R.; Torres, M.; Mancuso, N.; Berndt, S. I.; Van Den Eeden, S. K.; Easton, D. F.; Chanock, S. J.; Cook, M. B.; Wiklund, F.; Nakagawa, H.; Witte, J. S.; Eeles, R. A.; Kote-Jarai, Z.; Haiman, C. A.

Authors

Conti, D. V.
Darst, B. F.
Moss, L. C.
Saunders, E. J.
Sheng, X.
Chou, A.
Schumacher, F. R.
Olama, A. A. A.
Benlloch, S.
Dadaev, T.

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Affiliation

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.

Issue Date

2021

Metadata

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Abstract

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.

Citation

Conti DV, Darst BF, Moss LC, Saunders EJ, Sheng X, Chou A, et al. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nat Genet. 2021;53(1):65-75.

Journal

Nature Genetics

URI

http://hdl.handle.net/10541/623743

DOI

10.1038/s41588-020-00748-0

PubMed ID

33398198

Additional Links

https://dx.doi.org/10.1038/s41588-020-00748-0

Type

Article

Language

Collections

All Paterson Institute for Cancer Research

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
Authors: Al Olama AA, Kote-Jarai Z, Berndt SI, Conti DV, Schumacher F, Han Y, Benlloch S, Hazelett DJ, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Stram DO, Rand K, Wan P, Stram A, Sheng X, Pooler LC, Park K, Xia L, Tyrer J, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tammela TL, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Leinonen KA, Xu J, Aly M, Donovan J, Travis RC, Key TJ, Siddiq A, Canzian F, Khaw KT, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Nordestgaard BG, Nielsen SF, Klarskov P, Røder MA, Iversen P, Thibodeau SN, McDonnell SK, Schaid DJ, Stanford JL, Kolb S, Holt S, Knudsen B, Coll AH, Gapstur SM, Diver WR, Stevens VL, Maier C, Luedeke M, Herkommer K, Rinckleb AE, Strom SS, Pettaway C, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Cannon-Albright L, Cybulski C, Wokołorczyk D, Kluźniak W, Park J, Sellers T, Lin HY, Isaacs WB, Partin AW, Brenner H, Dieffenbach AK, Stegmaier C, Chen C, Giovannucci EL, Ma J, Stampfer M, Penney KL, Mucci L, John EM, Ingles SA, Kittles RA, Murphy AB, Pandha H, Michael A, Kierzek AM, Blot W, Signorello LB, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske C, Wu SY, Hennis A, Kibel AS, Rybicki BA, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Batra J, Clements J, Spurdle A, Teixeira MR, Paulo P, Maia S, Slavov C, Kaneva R, Mitev V, Witte JS, Casey G, Gillanders EM, Seminara D, Riboli E, Hamdy FC, Coetzee GA, Li Q, Freedman ML, Hunter DJ, Muir K, Gronberg H, Neal DE, Southey M, Giles GG, Severi G, Breast and Prostate Cancer Cohort Consortium (BPC3), PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, COGS (Collaborative Oncological Gene-environment Study) Consortium, GAME-ON/ELLIPSE Consortium, Cook MB, Nakagawa H, Wiklund F, Kraft P, Chanock SJ, Henderson BE, Easton DF, Eeles RA, Haiman CA
Issue date: 2014 Oct

Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.
Authors: Wang A, Shen J, Rodriguez AA, Saunders EJ, Chen F, Janivara R, Darst BF, Sheng X, Xu Y, Chou AJ, Benlloch S, Dadaev T, Brook MN, Plym A, Sahimi A, Hoffman TJ, Takahashi A, Matsuda K, Momozawa Y, Fujita M, Laisk T, Figuerêdo J, Muir K, Ito S, Liu X, Biobank Japan Project, Uchio Y, Kubo M, Kamatani Y, Lophatananon A, Wan P, Andrews C, Lori A, Choudhury PP, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Giles GG, Southey MC, MacInnis RJ, Cybulski C, Wokolorczyk D, Lubinski J, Rentsch CT, Cho K, Mcmahon BH, Neal DE, Donovan JL, Hamdy FC, Martin RM, Nordestgaard BG, Nielsen SF, Weischer M, Bojesen SE, Røder A, Stroomberg HV, Batra J, Chambers S, Horvath L, Clements JA, Tilly W, Risbridger GP, Gronberg H, Aly M, Szulkin R, Eklund M, Nordstrom T, Pashayan N, Dunning AM, Ghoussaini M, Travis RC, Key TJ, Riboli E, Park JY, Sellers TA, Lin HY, Albanes D, Weinstein S, Cook MB, Mucci LA, Giovannucci E, Lindstrom S, Kraft P, Hunter DJ, Penney KL, Turman C, Tangen CM, Goodman PJ, Thompson IM Jr, Hamilton RJ, Fleshner NE, Finelli A, Parent MÉ, Stanford JL, Ostrander EA, Koutros S, Beane Freeman LE, Stampfer M, Wolk A, Håkansson N, Andriole GL, Hoover RN, Machiela MJ, Sørensen KD, Borre M, Blot WJ, Zheng W, Yeboah ED, Mensah JE, Lu YJ, Zhang HW, Feng N, Mao X, Wu Y, Zhao SC, Sun Z, Thibodeau SN, McDonnell SK, Schaid DJ, West CML, Barnett G, Maier C, Schnoeller T, Luedeke M, Kibel AS, Drake BF, Cussenot O, Cancel-Tassin G, Menegaux F, Truong T, Koudou YA, John EM, Grindedal EM, Maehle L, Khaw KT, Ingles SA, Stern MC, Vega A, Gómez-Caamaño A, Fachal L, Rosenstein BS, Kerns SL, Ostrer H, Teixeira MR, Paulo P, Brandão A, Watya S, Lubwama A, Bensen JT, Butler EN, Mohler JL, Taylor JA, Kogevinas M, Dierssen-Sotos T, Castaño-Vinyals G, Cannon-Albright L, Teerlink CC, Huff CD, Pilie P, Yu Y, Bohlender RJ, Gu J, Strom SS, Multigner L, Blanchet P, Brureau L, Kaneva R, Slavov C, Mitev V, Leach RJ, Brenner H, Chen X, Holleczek B, Schöttker B, Klein EA, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Kim J, Neuhausen SL, Steele L, Ding YC, Isaacs WB, Nemesure B, Hennis AJM, Carpten J, Pandha H, Michael A, De Ruyck K, De Meerleer G, Ost P, Xu J, Razack A, Lim J, Teo SH, Newcomb LF, Lin DW, Fowke JH, Neslund-Dudas CM, Rybicki BA, Gamulin M, Lessel D, Kulis T, Usmani N, Abraham A, Singhal S, Parliament M, Claessens F, Joniau S, Van den Broeck T, Gago-Dominguez M, Castelao JE, Martinez ME, Larkin S, Townsend PA, Aukim-Hastie C, Bush WS, Aldrich MC, Crawford DC, Srivastava S, Cullen J, Petrovics G, Casey G, Wang Y, Tettey Y, Lachance J, Tang W, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Yamoah K, Govindasami K, Chokkalingam AP, Keaton JM, Hellwege JN, Clark PE, Jalloh M, Gueye SM, Niang L, Ogunbiyi O, Shittu O, Amodu O, Adebiyi AO, Aisuodionoe-Shadrach OI, Ajibola HO, Jamda MA, Oluwole OP, Nwegbu M, Adusei B, Mante S, Darkwa-Abrahams A, Diop H, Gundell SM, Roobol MJ, Jenster G, van Schaik RHN, Hu JJ, Sanderson M, Kachuri L, Varma R, McKean-Cowdin R, Torres M, Preuss MH, Loos RJF, Zawistowski M, Zöllner S, Lu Z, Van Den Eeden SK, Easton DF, Ambs S, Edwards TL, Mägi R, Rebbeck TR, Fritsche L, Chanock SJ, Berndt SI, Wiklund F, Nakagawa H, Witte JS, Gaziano JM, Justice AC, Mancuso N, Terao C, Eeles RA, Kote-Jarai Z, Madduri RK, Conti DV, Haiman CA
Issue date: 2023 Dec