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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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The Heritability of Breast Cancer among Women in the Nordic Twin Study of Cancer

Sören Möller, Lorelei A. Mucci, Jennifer R. Harris, Thomas Scheike, Klaus Holst, Ulrich Halekoh, Hans-Olov Adami, Kamila Czene, Kaare Christensen, Niels V. Holm, Eero Pukkala, Axel Skytthe, Jaakko Kaprio and Jacob B. Hjelmborg
Sören Möller
1Epidemiology, Biostatistics, and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
2The Danish Twin Registry, University of Southern Denmark, Odense, Denmark.
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  • For correspondence: moeller@health.sdu.dk
Lorelei A. Mucci
3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
4Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
5Centre for Public Health Sciences, University of Iceland, Reykjavik, Iceland.
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Jennifer R. Harris
6Division of Epidemiology, The Norwegian Institute of Public Health, Oslo, Norway.
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Thomas Scheike
7Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
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Klaus Holst
7Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
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Ulrich Halekoh
1Epidemiology, Biostatistics, and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
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Hans-Olov Adami
3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
8Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Kamila Czene
8Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Kaare Christensen
1Epidemiology, Biostatistics, and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
2The Danish Twin Registry, University of Southern Denmark, Odense, Denmark.
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Niels V. Holm
2The Danish Twin Registry, University of Southern Denmark, Odense, Denmark.
9Department of Oncology, Odense University Hospital, Odense, Denmark.
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Eero Pukkala
10Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.
11School of Health Sciences, University of Tampere, Tampere, Finland.
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Axel Skytthe
1Epidemiology, Biostatistics, and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
2The Danish Twin Registry, University of Southern Denmark, Odense, Denmark.
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Jaakko Kaprio
12Department of Public Health & Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
13Department of Health, National Institute for Health & Welfare, Helsinki, Finland.
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Jacob B. Hjelmborg
1Epidemiology, Biostatistics, and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
2The Danish Twin Registry, University of Southern Denmark, Odense, Denmark.
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DOI: 10.1158/1055-9965.EPI-15-0913 Published January 2016
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Abstract

Background: Family history is an established risk factor for breast cancer. Although some important genetic factors have been identified, the extent to which familial risk can be attributed to genetic factors versus common environment remains unclear.

Methods: We estimated the familial concordance and heritability of breast cancer among 21,054 monozygotic and 30,939 dizygotic female twin pairs from the Nordic Twin Study of Cancer, the largest twin study of cancer in the world. We accounted for left-censoring, right-censoring, as well as the competing risk of death.

Results: From 1943 through 2010, 3,933 twins were diagnosed with breast cancer. The cumulative lifetime incidence of breast cancer taking competing risk of death into account was 8.1% for both zygosities, although the cumulative risk for twins whose co-twins had breast cancer was 28% among monozygotic and 20% among dizygotic twins. The heritability of liability to breast cancer was 31% [95% confidence interval (CI), 10%–51%] and the common environmental component was 16% (95% CI, 10%–32%). For premenopausal breast cancer these estimates were 27% and 12%, respectively, and for postmenopausal breast cancer 22% and 16%, respectively. The relative contributions of genetic and environmental factors were constant between ages 50 and 96. Our results are compatible with the Peto–Mack hypothesis.

Conclusion: Our findings indicate that familial factors explain almost half of the variation in liability to develop breast cancer, and results were similar for pre- and postmenopausal breast cancer

Impact: We estimate heritability of breast cancer, taking until now ignored sources of bias into account. Cancer Epidemiol Biomarkers Prev; 25(1); 145–50. ©2015 AACR.

  • Received August 27, 2015.
  • Revision received October 26, 2015.
  • Accepted October 28, 2015.
  • ©2015 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 25 (1)
January 2016
Volume 25, Issue 1
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The Heritability of Breast Cancer among Women in the Nordic Twin Study of Cancer
Sören Möller, Lorelei A. Mucci, Jennifer R. Harris, Thomas Scheike, Klaus Holst, Ulrich Halekoh, Hans-Olov Adami, Kamila Czene, Kaare Christensen, Niels V. Holm, Eero Pukkala, Axel Skytthe, Jaakko Kaprio and Jacob B. Hjelmborg
Cancer Epidemiol Biomarkers Prev January 1 2016 (25) (1) 145-150; DOI: 10.1158/1055-9965.EPI-15-0913

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The Heritability of Breast Cancer among Women in the Nordic Twin Study of Cancer
Sören Möller, Lorelei A. Mucci, Jennifer R. Harris, Thomas Scheike, Klaus Holst, Ulrich Halekoh, Hans-Olov Adami, Kamila Czene, Kaare Christensen, Niels V. Holm, Eero Pukkala, Axel Skytthe, Jaakko Kaprio and Jacob B. Hjelmborg
Cancer Epidemiol Biomarkers Prev January 1 2016 (25) (1) 145-150; DOI: 10.1158/1055-9965.EPI-15-0913
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