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