The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer.

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 - 2014/11/1

Y1 - 2014/11/1

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 (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 forMZthan DZpairs (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. Impact: Findings affect 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 (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 forMZthan DZpairs (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. Impact: Findings affect 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

SN - 1055-9965

VL - 23

SP - 2303

EP - 2310

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 11

ER -