Article open access publication

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 9, 1, 2018

DOI:10.1038/s41467-018-06863-1, Dimensions: pub.1107926132, PMC: PMC6218483, PMID: 30397198,

Authors

Wang, Kan (1)
Benlloch, Sara (2) (3)
Muir, Kenneth (7) (8)
Batra, Jyotsna (11) (12)
Clements, Judith (11) (12)
Pashayan, Nora (3) (14)
Schleutker, Johanna (15) (16) (17)
Neal, David E. (3) (26)
Giles, Graham G (32) (33)
Vega, Ana (35)
Kogevinas, Manolis (37) (38) (39) (40)
Stanford, Janet L (10) (42)
Kim, Jeri (25)
Newcomb, Lisa F (10) (42)

* Corresponding author

Affiliations

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  1. (1) University of Southern California, grid.42505.36
  2. (2) Institute of Cancer Research, grid.18886.3f
  3. (3) University of Cambridge, grid.5335.0
  4. (4) Case Western Reserve University, grid.67105.35
  5. (5) University Hospitals of Cleveland, grid.241104.2
  6. (6) National Institute of Arthritis and Musculoskeletal and Skin Diseases, grid.420086.8
  7. (7) University of Warwick, grid.7372.1
  8. (8) University of Manchester, grid.5379.8
  9. (9) American Cancer Society, grid.422418.9
  10. (10) Fred Hutchinson Cancer Research Center, grid.270240.3
  11. (11) Queensland University of Technology, grid.1024.7
  12. (12) Translational Research Institute, grid.489335.0
  13. (13) Karolinska Institute, grid.4714.6
  14. (14) University College London, grid.83440.3b
  15. (15) Tampere University, grid.502801.e
  16. (16) Turku University Hospital, grid.410552.7
  17. (17) University of Turku, grid.1374.1
  18. (18) Division of Cancer Sciences, Manchester Academic Health Science Centre, Radiotherapy Related Research, Manchester NIHR Biomedical Research Centre, The Christie Hospital NHS Foundation Trust, University of Manchester, M13 9PL, Manchester, UK
  19. (19) Harvard University, grid.38142.3c
  20. (20) GRC N°5 ONCOTYPE-URO, UPMC Univ Paris 06, Tenon Hospital, F-75020, Paris, France
  21. (21) Tenon Hospital, grid.413483.9
  22. (22) Aarhus University, grid.7048.b, AU
  23. (23) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  24. (24) Oslo University Hospital, grid.55325.34
  25. (25) The University of Texas MD Anderson Cancer Center, grid.240145.6
  26. (26) Cancer Research UK Cambridge Institute, grid.470869.4
  27. (27) University of Oxford, grid.4991.5
  28. (28) University of Bristol, grid.5337.2
  29. (29) Princess Margaret Cancer Centre, grid.415224.4
  30. (30) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  31. (31) Queen Mary University of London, grid.4868.2
  32. (32) Cancer Council Victoria, grid.3263.4
  33. (33) University of Melbourne, grid.1008.9
  34. (34) Brigham and Women's Hospital, grid.62560.37
  35. (35) Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica, CIBERER, IDIS, 15706, Santiago de Compostela, Spain
  36. (36) Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, 29208, Columbia, SC, USA
  37. (37) Center for Research in Environmental Epidemiology, grid.417617.2
  38. (38) Hospital Del Mar, grid.411142.3
  39. (39) Institute of Health Carlos III, grid.413448.e
  40. (40) Pompeu Fabra University, grid.5612.0
  41. (41) Moffitt Cancer Center, grid.468198.a
  42. (42) University of Washington, grid.34477.33
  43. (43) Pomeranian Medical University, grid.107950.a
  44. (44) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2200, Copenhagen, Denmark
  45. (45) University of Copenhagen, grid.5254.6, KU
  46. (46) German Cancer Research Center, grid.7497.d
  47. (47) University Hospital Ulm, grid.410712.1
  48. (48) Department of Genetics, Portuguese Oncology Institute of Porto, 4200-072, Porto, Portugal
  49. (49) University of Porto, grid.5808.5
  50. (50) City Of Hope National Medical Center, grid.410425.6
  51. (51) Ghent University, grid.5342.0
  52. (52) University of Malaya, grid.10347.31
  53. (53) University Medical Center Hamburg-Eppendorf, grid.13648.38
  54. (54) Medical University of Sofia, grid.410563.5
  55. (55) University of Alberta, grid.17089.37
  56. (56) KU Leuven, grid.5596.f
  57. (57) Complejo Hospitalario Universitario de Santiago, grid.411048.8
  58. (58) University of California, San Diego, grid.266100.3
  59. (59) Erasmus University Medical Center, grid.5645.2
  60. (60) Cancer and Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, 94807, Villejuif Cédex, France
  61. (61) George E. Wahlen Department of VA Medical Center, grid.413886.0
  62. (62) University of Utah, grid.223827.e
  63. (63) University of Surrey, grid.5475.3
  64. (64) Mayo Clinic, grid.66875.3a
  65. (65) Royal Marsden NHS Foundation Trust, grid.5072.0

Description

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.

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Danish Open Access Indicator

2018: Realized

Research area: Medicine

Danish Bibliometrics Indicator

2018: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 16

Field Citation Ratio (FCR): 8

Relative Citation ratio (RCR): 1.05

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