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

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, Lorelei A Mucci

Research output: Contribution to journalJournal articleResearchpeer-review

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 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.
Original languageEnglish
JournalCancer Epidemiology, Biomarkers & Prevention
Volume23
Issue number11
Pages (from-to)2303-2310
ISSN1055-9965
DOIs
Publication statusPublished - Nov 2014

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Twin Studies
Prostatic Neoplasms
Neoplasms
Genetic Heterogeneity
Genetic Markers
Epigenomics
Population
Prospective Studies

Keywords

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Bias
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Models, Statistical
  • Prospective Studies
  • Prostatic Neoplasms/diagnosis
  • Registries
  • Risk Assessment
  • Scandinavian and Nordic Countries/epidemiology
  • Time Factors
  • Twins, Dizygotic/genetics
  • Twins, Monozygotic/genetics

Cite this

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. / The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer. In: Cancer Epidemiology, Biomarkers & Prevention. 2014 ; Vol. 23, No. 11. pp. 2303-2310.
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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 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 andliability.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.",
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author = "Hjelmborg, {Jacob B} and Thomas Scheike and Klaus Holst and Axel Skytthe and Penney, {Kathryn L} and Graff, {Rebecca E} and Eero Pukkala and Kaare Christensen and Hans-Olov Adami and Holm, {Niels V} and Elizabeth Nuttall and Steinbjorn Hansen and Mikael Hartman and Kamila Czene and Harris, {Jennifer R} and Jaakko Kaprio and Mucci, {Lorelei A}",
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Hjelmborg, JB, Scheike, T, Holst, K, Skytthe, A, Penney, KL, Graff, RE, Pukkala, E, Christensen, K, Adami, H-O, Holm, NV, Nuttall, E, Hansen, S, Hartman, M, Czene, K, Harris, JR, Kaprio, J & Mucci, LA 2014, 'The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer', Cancer Epidemiology, Biomarkers & Prevention, vol. 23, no. 11, pp. 2303-2310. https://doi.org/10.1158/1055-9965.EPI-13-0568

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 journalJournal articleResearchpeer-review

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

N1 - ©2014 American Association for Cancer Research.

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 andliability.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 andliability.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.

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Bias

KW - Humans

KW - Incidence

KW - Male

KW - Middle Aged

KW - Models, Statistical

KW - Prospective Studies

KW - Prostatic Neoplasms/diagnosis

KW - Registries

KW - Risk Assessment

KW - Scandinavian and Nordic Countries/epidemiology

KW - Time Factors

KW - Twins, Dizygotic/genetics

KW - Twins, Monozygotic/genetics

U2 - 10.1158/1055-9965.EPI-13-0568

DO - 10.1158/1055-9965.EPI-13-0568

M3 - Journal article

VL - 23

SP - 2303

EP - 2310

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 11

ER -