Article open access publication

Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 50, 7, 2018

DOI:10.1038/s41588-018-0142-8, Dimensions: pub.1104478461, PMC: PMC6568012, PMID: 29892016,

Authors

Benlloch, Sara (3) (5)
Goh, Chee (5)
Fachal, Laura (3) (7)
Muir, Kenneth (8) (9)
Batra, Jyotsna (13) (14)
Chambers, Suzanne (15) (16)
Moya, Leire (13) (14)
Clements, Judith (13) (14)
Horvath, Lisa (17) (18)
Aly, Markus (22) (23)
Pashayan, Nora (3) (24)
Wolk, Alicja (22) (28)
Borre, Michael (32) (33)
Neal, David E. (3) (35) (36)
Guo, Xin (45)
Sun, Zan (47)
Giles, Graham G (48) (49)
Vega, Ana (7)
Szulkin, Robert (22) (53)
Kogevinas, Manolis (54) (55) (56) (57)
Llorca, Javier (54) (58)
Castaño-Vinyals, Gemma (54) (55) (56) (57)
Stanford, Janet L (11) (61)
Nielsen, Sune F. (64) (65)
Kim, Jeri (71)
John, Esther M (72) (73)
Lin, Daniel W (11) (61)
Newcomb, Lisa F (11) (61)
Ma, Jing (51)
Cui, Zuxi (2)
Amos, Christopher I (99) (100)
Eeles, Rosalind A. * (5) (101)

* Corresponding author

Affiliations

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  1. (1) University Hospitals of Cleveland, grid.241104.2
  2. (2) Case Western Reserve University, grid.67105.35
  3. (3) University of Cambridge, grid.5335.0
  4. (4) National Institute of Arthritis and Musculoskeletal and Skin Diseases, grid.420086.8
  5. (5) Institute of Cancer Research, grid.18886.3f
  6. (6) University of Southern California, grid.42505.36
  7. (7) Fundación Pública Galega de Medicina Xenómica–SERGAS, Grupo de Medicina Xenómica, CIBERER, IDIS, Santiago de Compostela, Spain
  8. (8) University of Warwick, grid.7372.1
  9. (9) University of Manchester, grid.5379.8
  10. (10) American Cancer Society, grid.422418.9
  11. (11) Fred Hutchinson Cancer Research Center, grid.270240.3
  12. (12) CHRISTUS Santa Rosa Hospital–Medical Center, San Antonio, TX, USA
  13. (13) Queensland University of Technology, grid.1024.7
  14. (14) Translational Research Institute, grid.489335.0
  15. (15) Cancer Council Queensland, grid.430282.f
  16. (16) Griffith University, grid.1022.1
  17. (17) Chris O’Brien Lifehouse, grid.419783.0
  18. (18) Garvan Institute of Medical Research, grid.415306.5
  19. (19) University of Adelaide, grid.1010.0
  20. (20) Peter MacCallum Cancer Centre, grid.1055.1
  21. (21) Monash University, grid.1002.3
  22. (22) Karolinska Institute, grid.4714.6
  23. (23) Karolinska University Hospital, grid.24381.3c
  24. (24) University College London, grid.83440.3b
  25. (25) Turku University Hospital, grid.410552.7
  26. (26) University of Turku, grid.1374.1
  27. (27) Tampere University, grid.502801.e
  28. (28) Uppsala University, grid.8993.b
  29. (29) Harvard University, grid.38142.3c
  30. (30) Washington University in St. Louis, grid.4367.6
  31. (31) Tenon Hospital, grid.413483.9
  32. (32) Aarhus University, grid.7048.b, AU
  33. (33) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  34. (34) Oslo University Hospital, grid.55325.34
  35. (35) Cancer Research UK Cambridge Institute, grid.470869.4
  36. (36) University of Oxford, grid.4991.5
  37. (37) University of Bristol, grid.5337.2
  38. (38) Princess Margaret Cancer Centre, grid.415224.4
  39. (39) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  40. (40) University of Rochester Medical Center, grid.412750.5
  41. (41) Albert Einstein College of Medicine, grid.251993.5
  42. (42) Queen Mary University of London, grid.4868.2
  43. (43) Second Military Medical University, grid.73113.37
  44. (44) Nanjing Medical University, grid.89957.3a
  45. (45) Chongqing Medical University, grid.203458.8
  46. (46) Zhongshan Hospital, grid.413087.9
  47. (47) Liaoning Provincial People's Hospital, grid.452816.c
  48. (48) University of Melbourne, grid.1008.9
  49. (49) Cancer Council Victoria, grid.3263.4
  50. (50) University of Tasmania, grid.1009.8
  51. (51) Brigham and Women's Hospital, grid.62560.37
  52. (52) Complejo Hospitalario Universitario de Santiago, grid.411048.8
  53. (53) Scandinavian Development Services, Danderyd, Sweden
  54. (54) Institute of Health Carlos III, grid.413448.e
  55. (55) Hospital Del Mar, grid.411142.3
  56. (56) ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
  57. (57) Pompeu Fabra University, grid.5612.0
  58. (58) University of Cantabria, grid.7821.c
  59. (59) Moffitt Cancer Center, grid.468198.a
  60. (60) Louisiana State University Health Sciences Center New Orleans, grid.279863.1
  61. (61) University of Washington, grid.34477.33
  62. (62) Pomeranian Medical University, grid.107950.a
  63. (63) National Human Genome Research Institute, grid.280128.1
  64. (64) University of Copenhagen, grid.5254.6, KU
  65. (65) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  66. (66) Department of Urology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  67. (67) Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  68. (68) German Cancer Research Center, grid.7497.d
  69. (69) Krebsregister Saarland, grid.482902.5
  70. (70) University Hospital Ulm, grid.410712.1
  71. (71) The University of Texas MD Anderson Cancer Center, grid.240145.6
  72. (72) Cancer Prevention Institute of California, grid.280669.3
  73. (73) Stanford University, grid.168010.e
  74. (74) University of Porto, grid.5808.5
  75. (75) Department of Genetics, Portuguese Oncology Institute of Porto, Porto, Portugal
  76. (76) City Of Hope National Medical Center, grid.410425.6
  77. (77) Ghent University, grid.5342.0
  78. (78) Ghent University Hospital, grid.410566.0
  79. (79) University of Malaya, grid.10347.31
  80. (80) Cancer Research Malaysia (CRM), Outpatient Centre, Subang Jaya Medical Centre, Selangor, Malaysia
  81. (81) University Medical Center Hamburg-Eppendorf, grid.13648.38
  82. (82) University Hospital Centre Zagreb, grid.412688.1
  83. (83) Medical University of Sofia, grid.410563.5
  84. (84) University of Alberta, grid.17089.37
  85. (85) KU Leuven, grid.5596.f
  86. (86) Universitair Ziekenhuis Leuven, grid.410569.f
  87. (87) University of Southampton, Southampton General Hospital, Southampton, UK
  88. (88) University of Surrey, grid.5475.3
  89. (89) University of California, San Diego, grid.266100.3
  90. (90) University Hospital Complex Of Vigo, grid.411855.c
  91. (91) Erasmus University Medical Center, grid.5645.2
  92. (92) Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
  93. (93) NorthShore University HealthSystem, grid.240372.0
  94. (94) George E. Wahlen Department of VA Medical Center, grid.413886.0
  95. (95) University of Utah, grid.223827.e
  96. (96) Mayo Clinic, grid.66875.3a
  97. (97) Imperial College London, grid.7445.2
  98. (98) University of Hawaii at Manoa, grid.410445.0
  99. (99) Dartmouth College, grid.254880.3
  100. (100) Dartmouth–Hitchcock Medical Center, grid.413480.a
  101. (101) Royal Marsden NHS Foundation Trust, grid.5072.0

Description

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.

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Danish Open Access Indicator

2018: Realized

Research area: Medicine

Danish Bibliometrics Indicator

2018: Level 3

Research area: Medicine

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Times Cited: 156

Field Citation Ratio (FCR): 99.49

Relative Citation ratio (RCR): 12.4

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Green, Accepted