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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Author

Listed:
  • Alexander Gusev

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health
    Broad Institute of Harvard and MIT)

  • Huwenbo Shi

    (University of California Los Angeles)

  • Gleb Kichaev

    (University of California Los Angeles)

  • Mark Pomerantz

    (Dana-Farber Cancer Institute and Harvard Medical School)

  • Fugen Li

    (Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute
    Dana-Farber Cancer Institute)

  • Henry W. Long

    (Dana-Farber Cancer Institute and Harvard Medical School
    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute)

  • Sue A. Ingles

    (Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center)

  • Rick A. Kittles

    (University of Arizona College of Medicine and University of Arizona Cancer Center)

  • Sara S. Strom

    (University of Texas M.D. Anderson Cancer Center)

  • Benjamin A. Rybicki

    (Henry Ford Hospital)

  • Barbara Nemesure

    (Stony Brook University)

  • William B. Isaacs

    (James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution)

  • Wei Zheng

    (Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine)

  • Curtis A. Pettaway

    (University of Texas M.D. Anderson Cancer Center)

  • Edward D. Yeboah

    (Korle Bu Teaching Hospital
    University of Ghana Medical School)

  • Yao Tettey

    (Korle Bu Teaching Hospital
    University of Ghana Medical School)

  • Richard B. Biritwum

    (Korle Bu Teaching Hospital
    University of Ghana Medical School)

  • Andrew A. Adjei

    (Korle Bu Teaching Hospital
    University of Ghana Medical School)

  • Evelyn Tay

    (Korle Bu Teaching Hospital
    University of Ghana Medical School)

  • Ann Truelove

    (Westat)

  • Shelley Niwa

    (Westat)

  • Anand P. Chokkalingam

    (School of Public Health, University of California)

  • Esther M. John

    (Cancer Prevention Institute of California
    Stanford University School of Medicine and Stanford Cancer Institute)

  • Adam B. Murphy

    (Northwestern University)

  • Lisa B. Signorello

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health
    International Epidemiology Institute)

  • John Carpten

    (The Translational Genomics Research Institute)

  • M. Cristina Leske

    (Stony Brook University)

  • Suh-Yuh Wu

    (Stony Brook University)

  • Anslem J. M. Hennis

    (Stony Brook University
    Chronic Disease Research Centre and Faculty of Medical Sciences, University of the West Indies)

  • Christine Neslund-Dudas

    (Henry Ford Hospital)

  • Ann W. Hsing

    (Cancer Prevention Institute of California
    Stanford University School of Medicine and Stanford Cancer Institute)

  • Lisa Chu

    (Cancer Prevention Institute of California
    Stanford University School of Medicine and Stanford Cancer Institute)

  • Phyllis J. Goodman

    (SWOG Statistical Center, Fred Hutchinson Cancer Research Center)

  • Eric A. Klein

    (Glickman Urological & Kidney Institute, Cleveland Clinic)

  • John S. Witte

    (University of California, San Francisco
    Institute for Human Genetics, University of California, San Francisco)

  • Graham Casey

    (Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center)

  • Sam Kaggwa

    (Makerere University College of Health Sciences)

  • Michael B. Cook

    (National Cancer Institute)

  • Daniel O. Stram

    (Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center)

  • William J. Blot

    (Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine
    International Epidemiology Institute)

  • Rosalind A. Eeles

    (The Institute of Cancer Research
    Royal Marsden National Health Service (NHS) Foundation Trust)

  • Douglas Easton

    (Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Laboratory)

  • ZSofia Kote-Jarai

    (The Institute of Cancer Research)

  • Ali Amin Al Olama

    (Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Laboratory)

  • Sara Benlloch

    (Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Laboratory)

  • Kenneth Muir

    (Institute of Population Health, University of Manchester
    Warwick Medical School, University of Warwick)

  • Graham G. Giles

    (Cancer Epidemiology Centre, The Cancer Council Victoria
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne)

  • Melissa C. Southey

    (Genetic Epidemiology Laboratory, The University of Melbourne)

  • Liesel M. Fitzgerald

    (Cancer Epidemiology Centre, The Cancer Council Victoria)

  • Henrik Gronberg

    (Karolinska Institute)

  • Fredrik Wiklund

    (Karolinska Institute)

  • Markus Aly

    (Karolinska Institute
    Department of Clinical Sciences at Danderyds Hospital)

  • Brian E. Henderson

    (Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center)

  • Johanna Schleutker

    (University of Turku
    BioMediTech, University of Tampere and FimLab Laboratories)

  • Tiina Wahlfors

    (BioMediTech, University of Tampere and FimLab Laboratories)

  • Teuvo L. J. Tammela

    (Tampere University Hospital and Medical School, University of Tampere)

  • Børge G. Nordestgaard

    (Herlev Hospital, Copenhagen University Hospital
    Faculty of Health and Medical Sciences, University of Copenhagen)

  • Tim J. Key

    (Cancer Epidemiology
    University of Oxford)

  • Ruth C. Travis

    (Cancer Epidemiology
    University of Oxford)

  • David E. Neal

    (University of Cambridge, Addenbrooke's Hospital
    Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre)

  • Jenny L. Donovan

    (School of Social and Community Medicine, University of Bristol, Canynge Hall)

  • Freddie C. Hamdy

    (Section for Epidemiology, Aarhus University
    Faculty of Medical Science, University of Oxford, John Radcliffe Hospital)

  • Paul Pharoah

    (Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Laboratory)

  • Nora Pashayan

    (Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Laboratory
    University College London)

  • Kay-Tee Khaw

    (Clinical Gerontology Unit, University of Cambridge)

  • Janet L. Stanford

    (Fred Hutchinson Cancer Research Center
    School of Public Health, University of Washington)

  • Stephen N. Thibodeau

    (Mayo Clinic)

  • Shannon K. McDonnell

    (Mayo Clinic)

  • Daniel J. Schaid

    (Mayo Clinic)

  • Christiane Maier

    (Institute of Human Genetics, University Hospital Ulm)

  • Walther Vogel

    (Institute of Human Genetics, University Hospital Ulm)

  • Manuel Luedeke

    (University Hospital Ulm)

  • Kathleen Herkommer

    (Klinikum rechts der Isar der Technischen Universitaet Muenchen)

  • Adam S. Kibel

    (Brigham and Womens Hospital, Dana-Farber Cancer Institute)

  • Cezary Cybulski

    (International Hereditary Cancer Center, Pomeranian Medical University)

  • Dominika Wokolorczyk

    (International Hereditary Cancer Center, Pomeranian Medical University)

  • Wojciech Kluzniak

    (International Hereditary Cancer Center, Pomeranian Medical University)

  • Lisa Cannon-Albright

    (University of Utah School of Medicine
    George E. Wahlen Department of Veterans Affairs Medical Center)

  • Craig Teerlink

    (University of Utah School of Medicine
    George E. Wahlen Department of Veterans Affairs Medical Center)

  • Hermann Brenner

    (German Cancer Research Center (DKFZ)
    German Cancer Consortium (DKTK))

  • Aida K. Dieffenbach

    (German Cancer Research Center (DKFZ)
    German Cancer Consortium (DKTK))

  • Volker Arndt

    (German Cancer Research Center (DKFZ))

  • Jong Y. Park

    (Moffitt Cancer Center)

  • Thomas A. Sellers

    (Moffitt Cancer Center)

  • Hui-Yi Lin

    (Biostatistics Program, Moffitt Cancer Center)

  • Chavdar Slavov

    (Medical University)

  • Radka Kaneva

    (Molecular Medicine Center, Medical University)

  • Vanio Mitev

    (Molecular Medicine Center, Medical University)

  • Jyotsna Batra

    (Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology)

  • Amanda Spurdle

    (Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research)

  • Judith A. Clements

    (Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology)

  • Manuel R. Teixeira

    (Portuguese Oncology Institute
    Biomedical Sciences Institute (ICBAS), University of Porto)

  • Hardev Pandha

    (The University of Surrey)

  • Agnieszka Michael

    (The University of Surrey)

  • Paula Paulo

    (Portuguese Oncology Institute)

  • Sofia Maia

    (Portuguese Oncology Institute)

  • Andrzej Kierzek

    (The University of Surrey)

  • David V. Conti

    (Norris Cancer Center, University of Southern California Keck School of Medicine)

  • Demetrius Albanes

    (Nutritional Epidemiology Branch, National Cancer Institute, US National Institute of Health)

  • Christine Berg

    (Johns Hopkins Medicine)

  • Sonja I. Berndt

    (National Cancer Institute)

  • Daniele Campa

    (Genomic Epidemiology Group, German Cancer Research Center (DKFZ))

  • E. David Crawford

    (Urologic Oncology, University of Colorado at Denver Health Sciences Center)

  • W. Ryan Diver

    (Epidemiology Research Program, American Cancer Society)

  • Susan M. Gapstur

    (Epidemiology Research Program, American Cancer Society)

  • J. Michael Gaziano

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health
    Harvard Medical School
    Brigham and Women's Hospital)

  • Edward Giovannucci

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health
    Harvard School of Public Health)

  • Robert Hoover

    (National Cancer Institute)

  • David J. Hunter

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health)

  • Mattias Johansson

    (International Agency for Research on Cancer
    Urology and Andrology, Umeå University)

  • Peter Kraft

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health
    Harvard School of Public Health)

  • Loic Le Marchand

    (Epidemiology Program, University of Hawaii Cancer Center)

  • Sara Lindström

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health
    Harvard School of Public Health)

  • Carmen Navarro

    (Regional Health Authority
    CIBER Epidemiología y Salud Pública (CIBERESP))

  • Kim Overvad

    (Johns Hopkins Medicine)

  • Elio Riboli

    (School of Public Health, Imperial College London)

  • Afshan Siddiq

    (School of Public Health, Imperial College London)

  • Victoria L. Stevens

    (Epidemiology Research Program, American Cancer Society)

  • Dimitrios Trichopoulos

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health
    Bureau of Epidemiologic Research, Academy of Athens
    Hellenic Health Foundation)

  • Paolo Vineis

    (HuGeF Foundation
    School of Public Health, Imperial College London)

  • Meredith Yeager

    (National Cancer Institute)

  • Gosia Trynka

    (Brigham and Women's Hospital and Harvard Medical School
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Soumya Raychaudhuri

    (Broad Institute of Harvard and MIT
    Brigham and Women's Hospital and Harvard Medical School
    Institute of Inflammation and Repair, University of Manchester)

  • Frederick R. Schumacher

    (Norris Cancer Center, University of Southern California Keck School of Medicine)

  • Alkes L. Price

    (Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health
    Broad Institute of Harvard and MIT)

  • Matthew L. Freedman

    (Broad Institute of Harvard and MIT
    Dana-Farber Cancer Institute and Harvard Medical School
    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute)

  • Christopher A. Haiman

    (Norris Cancer Center, University of Southern California Keck School of Medicine)

  • Bogdan Pasaniuc

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

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.

Suggested Citation

  • Alexander Gusev & Huwenbo Shi & Gleb Kichaev & Mark Pomerantz & Fugen Li & Henry W. Long & Sue A. Ingles & Rick A. Kittles & Sara S. Strom & Benjamin A. Rybicki & Barbara Nemesure & William B. Isaacs , 2016. "Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10979
    DOI: 10.1038/ncomms10979
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