The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer.
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The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer. / Hjelmborg, Jacob B; Scheike, Thomas; Holst, Klaus; Skytthe, Axel; Penney, Kathryn L; Graff, Rebecca E; Pukkala, Eero; Christensen, Kaare; Adami, Hans-Olov; Holm, Niels V; Nuttall, Elizabeth; Hansen, Steinbjorn; Hartman, Mikael; Czene, Kamila; Harris, Jennifer R; Kaprio, Jaakko; Mucci, Lorelei a.
In: Cancer Epidemiology, Biomarkers & Prevention, Vol. 23, No. 11, 11.2014, p. 2303-2310.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer.
AU - Hjelmborg, Jacob B
AU - Scheike, Thomas
AU - Holst, Klaus
AU - Skytthe, Axel
AU - Penney, Kathryn L
AU - Graff, Rebecca E
AU - Pukkala, Eero
AU - Christensen, Kaare
AU - Adami, Hans-Olov
AU - Holm, Niels V
AU - Nuttall, Elizabeth
AU - Hansen, Steinbjorn
AU - Hartman, Mikael
AU - Czene, Kamila
AU - Harris, Jennifer R
AU - Kaprio, Jaakko
AU - Mucci, Lorelei a
PY - 2014/11
Y1 - 2014/11
N2 - 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 and 30,054 dizygotic 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% CI 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 Impact: Findings impact the search for genetic and epigenetic markers and frame prevention efforts.
AB - 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 and 30,054 dizygotic 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% CI 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 Impact: Findings impact the search for genetic and epigenetic markers and frame prevention efforts.
U2 - 10.1158/1055-9965.EPI-13-0568
DO - 10.1158/1055-9965.EPI-13-0568
M3 - Journal article
C2 - 24812039
VL - 23
SP - 2303
EP - 2310
JO - Cancer Epidemiology, Biomarkers & Prevention
JF - Cancer Epidemiology, Biomarkers & Prevention
SN - 1055-9965
IS - 11
ER -
ID: 136449794