• Jacob B Hjelmborg, Thomas Scheike, Klaus Holst, Axel Skytthe, Kathryn L Penney, Rebecca E Graff, Eero Pukkala, Kaare Christensen, Hans-Olov Adami, Niels V Holm, Elizabeth Nuttall, Steinbjorn Hansen, Mikael Hartman, Kamila Czene, Jennifer R Harris, Jaakko Kaprio, and Lorelei A Mucci.
• 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.
• Cancer Epidemiol. Biomarkers Prev. 2014 Nov 1; 23 (11): 2303-10.

BackgroundProstate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age.MethodsTo 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.ResultsThe 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.ConclusionsResults 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.ImpactFindings affect the search for genetic and epigenetic markers and frame prevention efforts.©2014 American Association for Cancer Research.

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