title: The heritability of prostate cancer in the Nordic Twin Study of Cancer.
abstract: BACKGROUND
  Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age.
  
  
  METHODS
  To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic (MZ) and 30,054 dizygotic (DZ) same-sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability.
  
  
  RESULTS
  The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median, 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability [heritability = 58% (95% confidence interval, 52%-63%)] of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary.
  
  
  CONCLUSIONS
  Results from the population-based twin cohort indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age.
  
  
  CONCLUSIONS
  Findings affect the search for genetic and epigenetic markers and frame prevention efforts.
authors.affiliation: Department of Epidemiology, Biostatistics, and Biodemography, Institute of Public Health, University of Southern Denmark. The Danish Twin Registry, University of Southern Denmark. jhjelmborg@health.sdu.dk.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Hjelmborg
authors.affiliation: Department of Biostatistics, University of Copenhagen.
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheike
authors.affiliation: Department of Biostatistics, University of Copenhagen.
authors.forename: Klaus
authors.initials: K
authors.lastname: Holst
authors.affiliation: Department of Epidemiology, Biostatistics, and Biodemography, Institute of Public Health, University of Southern Denmark. The Danish Twin Registry, University of Southern Denmark.
authors.forename: Axel
authors.initials: A
authors.lastname: Skytthe
authors.affiliation: Department of Epidemiology, Harvard School of Public Health. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Penney
authors.affiliation: Department of Epidemiology, Harvard School of Public Health.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Graff
authors.affiliation: Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research. School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.affiliation: Department of Epidemiology, Biostatistics, and Biodemography, Institute of Public Health, University of Southern Denmark. The Danish Twin Registry, University of Southern Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Department of Epidemiology, Harvard School of Public Health. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.affiliation: The Danish Twin Registry, University of Southern Denmark. Department of Oncology, Odense University Hospital, Denmark.
authors.forename: Niels V
authors.initials: NV
authors.lastname: Holm
authors.affiliation: Department of Epidemiology, Harvard School of Public Health.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nuttall
authors.affiliation: Department of Oncology, Odense University Hospital, Denmark.
authors.forename: Steinbjorn
authors.initials: S
authors.lastname: Hansen
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, National University Hospital and NUHS, Singapore. Division of Epidemiology, The Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Mikael
authors.initials: M
authors.lastname: Hartman
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.affiliation: Division of Epidemiology, The Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Harris
authors.affiliation: Department of Public Health and Institute for Molecular Medicine, University of Helsinki. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Department of Epidemiology, Harvard School of Public Health. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Centre for Public Health Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015982:Bias; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D012042:Registries; D018570:Risk Assessment; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D013997:Time Factors; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*