title: Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.
abstract: Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
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authors.affiliation: Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, California 90095, USA.
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authors.lastname: Shi
authors.affiliation: Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, California 90095, USA.
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authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Mark
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authors.lastname: Pomerantz
authors.affiliation: Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.|Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Fugen
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.|Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Henry W
authors.initials: HW
authors.lastname: Long
authors.affiliation: Department of Preventative Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
authors.forename: Sue A
authors.initials: SA
authors.lastname: Ingles
authors.affiliation: University of Arizona College of Medicine and University of Arizona Cancer Center, Tucson, Arizona 85721, USA.
authors.forename: Rick A
authors.initials: RA
authors.lastname: Kittles
authors.affiliation: Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Strom
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rybicki
authors.affiliation: Department of Preventive Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nemesure
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, Maryland 21205, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
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authors.initials: CA
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authors.affiliation: Korle Bu Teaching Hospital, Accra, Ghana.|University of Ghana Medical School, Accra, Ghana.
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authors.initials: ED
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authors.affiliation: Korle Bu Teaching Hospital, Accra, Ghana.|University of Ghana Medical School, Accra, Ghana.
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authors.lastname: Tettey
authors.affiliation: Korle Bu Teaching Hospital, Accra, Ghana.|University of Ghana Medical School, Accra, Ghana.
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authors.initials: RB
authors.lastname: Biritwum
authors.affiliation: Korle Bu Teaching Hospital, Accra, Ghana.|University of Ghana Medical School, Accra, Ghana.
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authors.affiliation: Korle Bu Teaching Hospital, Accra, Ghana.|University of Ghana Medical School, Accra, Ghana.
authors.forename: Evelyn
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authors.affiliation: Westat, Rockville, Maryland 20850, USA.
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authors.initials: A
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authors.affiliation: Westat, Rockville, Maryland 20850, USA.
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authors.initials: S
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authors.affiliation: School of Public Health, University of California, Berkeley, California 94720, USA.
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authors.affiliation: Cancer Prevention Institute of California, Fremont, California 94538, USA.|Stanford University School of Medicine and Stanford Cancer Institute, Palo Alto, California 94305, USA.
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authors.initials: EM
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authors.affiliation: Department of Urology, Northwestern University, Chicago, Illinois 60611, USA.
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authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.|International Epidemiology Institute, Rockville, Maryland 20850, USA.
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authors.affiliation: The Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
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authors.affiliation: Department of Preventive Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: M Cristina
authors.initials: MC
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authors.affiliation: Department of Preventive Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
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authors.initials: SY
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authors.affiliation: Department of Preventive Medicine, Stony Brook University, Stony Brook, New York 11794, USA.|Chronic Disease Research Centre and Faculty of Medical Sciences, University of the West Indies, Bridgetown, Barbados.
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authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan 48202, USA.
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authors.affiliation: Cancer Prevention Institute of California, Fremont, California 94538, USA.|Stanford University School of Medicine and Stanford Cancer Institute, Palo Alto, California 94305, USA.
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authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94118, USA.|Institute for Human Genetics, University of California, San Francisco, San Francisco, California 94118, USA.
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authors.affiliation: Department of Surgery, Makerere University College of Health Sciences, Kampala 94118, Uganda.
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
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authors.affiliation: The Institute of Cancer Research, Sutton SM2 5NG, UK.|Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, UK.
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authors.initials: RA
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
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authors.affiliation: The Institute of Cancer Research, Sutton SM2 5NG, UK.
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
authors.forename: Ali Amin
authors.initials: AA
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
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authors.affiliation: Institute of Population Health, University of Manchester, Manchester M13 9PL, UK.|Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
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authors.initials: K
authors.lastname: Muir
authors.affiliation: Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3004, Australia.
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authors.initials: GG
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authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia.
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authors.affiliation: Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia.
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authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 171 77, Sweden.
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authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 171 77, Sweden.
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authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 171 77, Sweden.|Department of Clinical Sciences at Danderyds Hospital, Stockholm 171 77, Sweden.
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authors.initials: BE
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authors.affiliation: Department of Medical Biochemistry and Genetics Institute of Biomedicine Kiinamyllynkatu 10, University of Turku, Turku FI-20014, Finland.|BioMediTech, University of Tampere and FimLab Laboratories, Tampere 33200, Finland.
authors.forename: Johanna
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authors.affiliation: BioMediTech, University of Tampere and FimLab Laboratories, Tampere 33200, Finland.
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authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev DK-2730, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 1165, Densmark.
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authors.affiliation: Cancer Epidemiology, Nuffield Department of Population Health; University of Oxford, Oxford OX3 7LF, UK.
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authors.affiliation: University of Cambridge, Department of Oncology, Addenbrooke's Hospital, Box 279, Hills Road, Cambridge CB2 0QQ.|Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
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authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
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authors.initials: JL
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authors.affiliation: Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus OX1 3PN, Denmark.|Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford OX1 3PN, UK.
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authors.identifier: http://orcid.org/0000-0001-8494-732X
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.|University College London, Department of Applied Health Research, 1-19 Torrington Place, London WC1E 7HB, UK.
authors.forename: Nora
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authors.affiliation: Clinical Gerontology Unit, University of Cambridge, Cambridge CB1 8RN, UK.
authors.forename: Kay-Tee
authors.initials: KT
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authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.|Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington 98109, USA.
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authors.initials: JL
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authors.affiliation: Mayo Clinic, Rochester, Minnesota 55905, USA.
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authors.affiliation: Mayo Clinic, Rochester, Minnesota 55905, USA.
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authors.affiliation: Mayo Clinic, Rochester, Minnesota 55905, USA.
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authors.initials: DJ
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authors.affiliation: Institute of Human Genetics, University Hospital Ulm, 89081 Ulm, Germany.
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authors.initials: C
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authors.affiliation: Institute of Human Genetics, University Hospital Ulm, 89081 Ulm, Germany.
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authors.affiliation: Department of Urology, University Hospital Ulm, 89081 Ulm, Germany.
authors.forename: Manuel
authors.initials: M
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authors.affiliation: Department of Urology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, 81675 Munich, Germany.
authors.forename: Kathleen
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authors.affiliation: Division of Urologic Surgery, Brigham and Womens Hospital, Dana-Farber Cancer Institute, 75 Francis Street, Boston, Massachusetts 02115, USA.
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authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
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authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
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authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
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authors.affiliation: Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.|George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah 84132, USA.
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authors.initials: L
authors.lastname: Cannon-Albright
authors.affiliation: Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.|George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah 84132, USA.
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authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.|German Cancer Consortium (DKTK), Heidelberg 69120, Germany.
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authors.initials: AK
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authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
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authors.initials: V
authors.lastname: Arndt
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
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authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
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authors.initials: TA
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authors.affiliation: Biostatistics Program, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
authors.forename: Hui-Yi
authors.initials: HY
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authors.affiliation: Department of Urology and Alexandrovska University Hospital, Medical University, Sofia 1431, Bulgaria.
authors.forename: Chavdar
authors.initials: C
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authors.affiliation: Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave Str., Sofia 1431, Bulgaria.
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authors.initials: R
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authors.affiliation: Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave Str., Sofia 1431, Bulgaria.
authors.forename: Vanio
authors.initials: V
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authors.affiliation: Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland 4000, Australia.
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authors.affiliation: Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4000, Australia.
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authors.affiliation: Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland 4000, Australia.
authors.forename: Judith A
authors.initials: JA
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authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Porto 4200, Portugal.|Biomedical Sciences Institute (ICBAS), University of Porto, Porto 4200, Portugal.
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authors.affiliation: The University of Surrey, Guildford, Surrey GU2 7XH, UK.
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authors.initials: H
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authors.affiliation: The University of Surrey, Guildford, Surrey GU2 7XH, UK.
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authors.initials: A
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authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Porto 4200, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Paulo
authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Porto 4200, Portugal.
authors.forename: Sofia
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authors.affiliation: The University of Surrey, Guildford, Surrey GU2 7XH, UK.
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authors.initials: A
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authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland 20892, USA.
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authors.initials: D
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authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Berg
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
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authors.initials: SI
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authors.affiliation: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
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authors.initials: D
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authors.affiliation: Urologic Oncology, University of Colorado at Denver Health Sciences Center, Denver, Colorado 80230, USA.
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authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
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authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
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authors.initials: SM
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authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.|Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.|Division of Aging, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.|Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Robert
authors.initials: R
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authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
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authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: International Agency for Research on Cancer, Lyon 69008, France.|Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå 907 36, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.|Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Peter
authors.initials: P
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authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.
authors.forename: Loic
authors.initials: L
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authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.|Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.affiliation: Department of Epidemiology, Regional Health Authority, Murcia 30009, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona 28029, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2AZ, UK.
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.affiliation: Department of Genomics of Common Disease, School of Public Health, Imperial College London, London SW7 2AZ, UK.
authors.forename: Afshan
authors.initials: A
authors.lastname: Siddiq
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Stevens
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.|Bureau of Epidemiologic Research, Academy of Athens, Athens 106 79, Greece.|Hellenic Health Foundation, Athens 106 79, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.affiliation: HuGeF Foundation, Torino 10126, Italy.|School of Public Health, Imperial College London, London SW7 2AZ, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.affiliation: Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
authors.forename: Gosia
authors.identifier: http://orcid.org/0000-0002-6955-9529
authors.initials: G
authors.lastname: Trynka
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.|Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Institute of Inflammation and Repair, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Soumya
authors.initials: S
authors.lastname: Raychaudhuri
authors.affiliation: Department of Preventive Medicine, Norris Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Schumacher
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
authors.forename: Alkes L
authors.initials: AL
authors.lastname: Price
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.|Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Freedman
authors.affiliation: Department of Preventive Medicine, Norris Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, California 90095, USA.|Departments of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA.|Department of Human Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Pasaniuc
mesh_terms: D000107:Acetylation; D001741:Black or African American; D001271:Atlases as Topic; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D040582:Inheritance Patterns; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D044465:White People
chemical_list: D006657:Histones