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Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2303-10. doi: 10.1158/1055-9965.EPI-13-0568. Epub 2014 May 8.

The heritability of prostate cancer in the Nordic Twin Study of Cancer.

Author information

1
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.
2
Department of Biostatistics, University of Copenhagen.
3
Department of Epidemiology, Biostatistics, and Biodemography, Institute of Public Health, University of Southern Denmark. The Danish Twin Registry, University of Southern Denmark.
4
Department of Epidemiology, Harvard School of Public Health. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
5
Department of Epidemiology, Harvard School of Public Health.
6
Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research. School of Health Sciences, University of Tampere, Tampere, Finland.
7
Department of Epidemiology, Harvard School of Public Health. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;
8
The Danish Twin Registry, University of Southern Denmark. Department of Oncology, Odense University Hospital, Denmark.
9
Department of Oncology, Odense University Hospital, Denmark.
10
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.
11
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;
12
Division of Epidemiology, The Norwegian Institute of Public Health, Oslo, Norway.
13
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.
14
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.

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.

IMPACT:

Findings affect the search for genetic and epigenetic markers and frame prevention efforts.

Comment in

PMID:
24812039
PMCID:
PMC4221420
DOI:
10.1158/1055-9965.EPI-13-0568
[Indexed for MEDLINE]
Free PMC Article

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