Germline variation at 8q24 and prostate cancer risk in men of European ancestry
Marco Matejcic
(1)
,
Edward J Saunders
(2)
,
Tokhir Dadaev
(2)
,
Mark N Brook
(2)
,
Kan Wang
(1)
,
Xin Sheng
(1)
,
Ali Amin Al Olama
(3, 4)
,
Fredrick R Schumacher
(5)
,
Sue A Ingles
(1)
,
Koveela Govindasami
(2)
,
Sara Benlloch
(2, 4)
,
Sonja I Berndt
(6)
,
Demetrius Albanes
(6)
,
Stella Koutros
(6)
,
Kenneth Muir
(7, 8)
,
Victoria L Stevens
,
Susan M Gapstur
,
Catherine M Tangen
(9)
,
Jyotsna Batra
(10, 11)
,
Judith Clements
(11, 10)
,
Henrik Grönberg
(12, 13)
,
Nora Pashayan
(4, 14)
,
Johanna Schleutker
(15, 16)
,
Alicja Wolk
(13, 17)
,
Catharine West
(18, 8)
,
Lorelei Mucci
(19)
,
Peter Kraft
(20)
,
Geraldine Cancel-Tassin
(21)
,
Karina D Sorensen
(22, 23)
,
Lovise Maehle
(24)
,
Eli M Grindedal
(24)
,
Sara S Strom
(25)
,
David E Neal
(26)
,
Freddie C. Hamdy
(27)
,
Jenny Donovan
(28)
,
Ruth Travis
(27)
,
Robert J Hamilton
,
Barry Rosenstein
(29)
,
Yong-Jie Lu
(30, 31)
,
Graham G Giles
(32)
,
Adam S Kibel
(33)
,
Ana Vega
(34)
,
Jeanette T Bensen
,
Manolis Kogevinas
(35, 36, 37, 38)
,
Kathryn L Penney
(33)
,
Jong Bok Park
,
Janet L. Stanford
(9, 39)
,
Cezary Cybulski
,
Børge G. Nordestgaard
,
Hermann Brenner
(40, 41)
,
Christiane Maier
(42)
,
Jeri Kim
(25)
,
Manuel R Teixeira
(43)
,
Susan Neuhausen
,
Kim de Ruyck
(44)
,
Azad Razack
(45)
,
Lisa F Newcomb
(9, 39)
,
Davor Lessel
(46)
,
Radka Kaneva
,
Nawaid Usmani
(47)
,
Frank Claessens
(48)
,
Paul Townsend
(18, 8)
,
Manuela G Dominguez
(49)
,
Monique J Roobol
(50)
,
Florence Menegaux
(51, 52)
,
Kay-Tee Khaw
(53)
,
Lisa A Cannon-Albright
(54)
,
Hardev Pandha
(55)
,
Stephen N. Thibodeau
(56)
,
Daniel J. Schaid
(56)
,
Fredrik Wiklund
(13)
,
Stephen Chanock
,
Douglas F. Easton
(53, 4)
,
Rosalind Eeles
(2, 57)
,
Zsofia Kote-Jarai
(2)
,
David V Conti
(1, 58)
,
Christopher Haiman
(58, 1)
1
Keck School of Medicine [Los Angeles]
2 The institute of cancer research [London]
3 Department of Clinical Neurosciences [Cambridge]
4 Centre for Cancer Genetic Epidemiology [Cambridge]
5 Case Western Reserve University [Cleveland]
6 NCI-NIH - National Cancer Institute [Bethesda]
7 Warwick Medical School
8 University of Manchester [Manchester]
9 FHCRC - Fred Hutchinson Cancer Research Center [Seattle]
10 IHBI - Institute of Health and Biomedical Innovation
11 QUT - Queensland University of Technology [Brisbane]
12 MEB - Department of Medical Epidemiology and Biostatistics
13 Karolinska Institutet [Stockholm]
14 UCL - University College of London [London]
15 University of Turku
16 University of Tampere [Finland]
17 IMM - The Institute of Environmental Medicine [Stockholm]
18 MAHSC - Manchester Academic Health Science Centre
19 Harvard School of Public Health
20 Harvard T.H. Chan School of Public Health
21 UPMC - Université Pierre et Marie Curie - Paris 6
22 Aarhus University Hospital
23 Aarhus University [Aarhus]
24 Oslo University Hospital [Oslo]
25 The University of Texas M.D. Anderson Cancer Center [Houston]
26 Addenbrooke's Hospital
27 University of Oxford
28 School of Social and Community Medicine [Bristol]
29 MSSM - Icahn School of Medicine at Mount Sinai [New York]
30 Centre for Molecular Oncology and Imaging
31 QMUL - Queen Mary University of London
32 University of Melbourne
33 BWH - Brigham & Women’s Hospital [Boston]
34 CIBER de Enfermedades Raras (CIBERER)
35 CREAL - Center for Research in Environmental Epidemiology
36 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
37 IMIM-Hospital del Mar
38 UPF - Universitat Pompeu Fabra [Barcelona]
39 University of Washington [Seattle]
40 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
41 NCT - National Center for Tumor Diseases [Dresden]
42 Universität Ulm - Ulm University [Ulm, Allemagne]
43 ICBAS - Instituto de Ciências Biomédicas de Abel Salazar
44 UGENT - Universiteit Gent = Ghent University
45 UM - University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie]
46 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
47 University of Alberta
48 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
49 UC San Diego - University of California [San Diego]
50 Erasmus MC - Erasmus University Medical Center [Rotterdam]
51 CESP - Centre de recherche en épidémiologie et santé des populations
52 Université Paris-Saclay
53 CAM - University of Cambridge [UK]
54 University of Utah School of Medicine [Salt Lake City]
55 UNIS - University of Surrey
56 Mayo Clinic [Rochester]
57 Royal Marsden NHS Foundation Trust
58 USC - University of Southern California
2 The institute of cancer research [London]
3 Department of Clinical Neurosciences [Cambridge]
4 Centre for Cancer Genetic Epidemiology [Cambridge]
5 Case Western Reserve University [Cleveland]
6 NCI-NIH - National Cancer Institute [Bethesda]
7 Warwick Medical School
8 University of Manchester [Manchester]
9 FHCRC - Fred Hutchinson Cancer Research Center [Seattle]
10 IHBI - Institute of Health and Biomedical Innovation
11 QUT - Queensland University of Technology [Brisbane]
12 MEB - Department of Medical Epidemiology and Biostatistics
13 Karolinska Institutet [Stockholm]
14 UCL - University College of London [London]
15 University of Turku
16 University of Tampere [Finland]
17 IMM - The Institute of Environmental Medicine [Stockholm]
18 MAHSC - Manchester Academic Health Science Centre
19 Harvard School of Public Health
20 Harvard T.H. Chan School of Public Health
21 UPMC - Université Pierre et Marie Curie - Paris 6
22 Aarhus University Hospital
23 Aarhus University [Aarhus]
24 Oslo University Hospital [Oslo]
25 The University of Texas M.D. Anderson Cancer Center [Houston]
26 Addenbrooke's Hospital
27 University of Oxford
28 School of Social and Community Medicine [Bristol]
29 MSSM - Icahn School of Medicine at Mount Sinai [New York]
30 Centre for Molecular Oncology and Imaging
31 QMUL - Queen Mary University of London
32 University of Melbourne
33 BWH - Brigham & Women’s Hospital [Boston]
34 CIBER de Enfermedades Raras (CIBERER)
35 CREAL - Center for Research in Environmental Epidemiology
36 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
37 IMIM-Hospital del Mar
38 UPF - Universitat Pompeu Fabra [Barcelona]
39 University of Washington [Seattle]
40 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
41 NCT - National Center for Tumor Diseases [Dresden]
42 Universität Ulm - Ulm University [Ulm, Allemagne]
43 ICBAS - Instituto de Ciências Biomédicas de Abel Salazar
44 UGENT - Universiteit Gent = Ghent University
45 UM - University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie]
46 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
47 University of Alberta
48 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
49 UC San Diego - University of California [San Diego]
50 Erasmus MC - Erasmus University Medical Center [Rotterdam]
51 CESP - Centre de recherche en épidémiologie et santé des populations
52 Université Paris-Saclay
53 CAM - University of Cambridge [UK]
54 University of Utah School of Medicine [Salt Lake City]
55 UNIS - University of Surrey
56 Mayo Clinic [Rochester]
57 Royal Marsden NHS Foundation Trust
58 USC - University of Southern California
Victoria L Stevens
- Fonction : Auteur
Susan M Gapstur
- Fonction : Auteur
Alicja Wolk
- Fonction : Auteur
- PersonId : 784020
- ORCID : 0000-0001-7387-6845
Peter Kraft
- Fonction : Auteur
- PersonId : 765918
- ORCID : 0000-0002-4472-8103
Robert J Hamilton
- Fonction : Auteur
Yong-Jie Lu
- Fonction : Auteur
- PersonId : 875014
Jeanette T Bensen
- Fonction : Auteur
Manolis Kogevinas
- Fonction : Auteur
- PersonId : 762958
- ORCID : 0000-0002-9605-0461
Jong Bok Park
- Fonction : Auteur
- PersonId : 1011271
Cezary Cybulski
- Fonction : Auteur
Børge G. Nordestgaard
- Fonction : Auteur
Susan Neuhausen
- Fonction : Auteur
- PersonId : 920693
Radka Kaneva
- Fonction : Auteur
Florence Menegaux
- Fonction : Auteur
- PersonId : 834323
Stephen Chanock
- Fonction : Auteur
- PersonId : 767922
- ORCID : 0000-0002-2324-3393
Résumé
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.
Origine : Publication financée par une institution
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