Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.
About this Publication
Title
Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.
Pubmed ID
27052111
(View this publication on the PubMed website)
Publication
Nat Commun. 2016 Apr; Volume 7: Pages 10979
Authors
Gusev A, Shi H, Kichaev G, Pomerantz M, Li F, Long HW, Ingles SA, Kittles RA, Strom SS, Rybicki BA, Nemesure B, Isaacs WB, Zheng W, Pettaway CA, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, ...show more Niwa S, Chokkalingam AP, John EM, Murphy AB, Signorello LB, Carpten J, Leske MC, Wu SY, Hennis AJ, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Witte JS, Casey G, Kaggwa S, Cook MB, Stram DO, Blot WJ, Eeles RA, Easton D, Kote-Jarai Z, Al Olama AA, Benlloch S, Muir K, Giles GG, Southey MC, Fitzgerald LM, Gronberg H, Wiklund F, Aly M, Henderson BE, Schleutker J, Wahlfors T, Tammela TL, Nordestgaard BG, Key TJ, Travis RC, Neal DE, Donovan JL, Hamdy FC, Pharoah P, Pashayan N, Khaw KT, Stanford JL, Thibodeau SN, McDonnell SK, Schaid DJ, Maier C, Vogel W, Luedeke M, Herkommer K, Kibel AS, Cybulski C, Wokolorczyk D, Kluzniak W, Cannon-Albright L, Teerlink C, Brenner H, Dieffenbach AK, Arndt V, Park JY, Sellers TA, Lin HY, Slavov C, Kaneva R, Mitev V, Batra J, Spurdle A, Clements JA, Teixeira MR, Pandha H, Michael A, Paulo P, Maia S, Kierzek A, PRACTICAL consortium, Conti DV, Albanes D, Berg C, Berndt SI, Campa D, Crawford ED, Diver WR, Gapstur SM, Gaziano JM, Giovannucci E, Hoover R, Hunter DJ, Johansson M, Kraft P, Le Marchand L, Lindström S, Navarro C, Overvad K, Riboli E, Siddiq A, Stevens VL, Trichopoulos D, Vineis P, Yeager M, Trynka G, Raychaudhuri S, Schumacher FR, Price AL, Freedman ML, Haiman CA, Pasaniuc B
Affiliations
- Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
- Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, California 90095, 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.
- Department of Preventative Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
- University of Arizona College of Medicine and University of Arizona Cancer Center, Tucson, Arizona 85721, USA.
- Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
- Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan 48202, USA.
- Department of Preventive Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
- James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, Maryland 21205, USA.
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
- Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
- Korle Bu Teaching Hospital, Accra, Ghana.
- Westat, Rockville, Maryland 20850, USA.
- School of Public Health, University of California, Berkeley, California 94720, USA.
- Cancer Prevention Institute of California, Fremont, California 94538, USA.
- Department of Urology, Northwestern University, Chicago, Illinois 60611, USA.
- The Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
- SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
- Glickman Urological &Kidney Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94118, USA.
- Department of Surgery, Makerere University College of Health Sciences, Kampala 94118, Uganda.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
- The Institute of Cancer Research, Sutton SM2 5NG, UK.
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
- Institute of Population Health, University of Manchester, Manchester M13 9PL, UK.
- Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia.
- Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 171 77, Sweden.
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90007, USA.
- 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.
- Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere 33200, Finland.
- Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev DK-2730, Denmark.
- Cancer Epidemiology, Nuffield Department of Population Health; University of Oxford, Oxford OX3 7LF, UK.
- University of Cambridge, Department of Oncology, Addenbrooke's Hospital, Box 279, Hills Road, Cambridge CB2 0QQ.
- School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
- Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus OX1 3PN, Denmark.
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
- Clinical Gerontology Unit, University of Cambridge, Cambridge CB1 8RN, UK.
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
- Mayo Clinic, Rochester, Minnesota 55905, USA.
- Institute of Human Genetics, University Hospital Ulm, 89081 Ulm, Germany.
- Department of Urology, University Hospital Ulm, 89081 Ulm, Germany.
- Department of Urology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, 81675 Munich, Germany.
- Division of Urologic Surgery, Brigham and Womens Hospital, Dana-Farber Cancer Institute, 75 Francis Street, Boston, Massachusetts 02115, USA.
- International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
- Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
- Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
- Biostatistics Program, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
- Department of Urology and Alexandrovska University Hospital, Medical University, Sofia 1431, Bulgaria.
- Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave Str., Sofia 1431, Bulgaria.
- 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.
- Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4000, Australia.
- Department of Genetics, Portuguese Oncology Institute, Porto 4200, Portugal.
- The University of Surrey, Guildford, Surrey GU2 7XH, UK.
- Department of Preventive Medicine, Norris Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
- Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland 20892, USA.
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, Maryland 21287, USA.
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
- Urologic Oncology, University of Colorado at Denver Health Sciences Center, Denver, Colorado 80230, USA.
- Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
- International Agency for Research on Cancer, Lyon 69008, France.
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.
- Department of Epidemiology, Regional Health Authority, Murcia 30009, Spain.
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2AZ, UK.
- Department of Genomics of Common Disease, School of Public Health, Imperial College London, London SW7 2AZ, UK.
- HuGeF Foundation, Torino 10126, Italy.
- Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
- Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
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.
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