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, Jacob B Hjelmborg

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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, while 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% CI 10% - 51%) and the common environmental component was 16% (95% CI 10% - 32%). For pre-menopausal 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 post-menopausal breast cancer Impact We estimate heritability of breast cancer, taking until now ignored sources of bias into account.

Original languageEnglish
JournalCancer Epidemiology, Biomarkers & Prevention
Volume25
Issue number1
Pages (from-to)145-50
ISSN1055-9965
DOIs
Publication statusPublished - Jan 2016

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Twin Studies
Neoplasms
Dizygotic Twins
Risk-Taking

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Möller, Sören ; Mucci, Lorelei A ; Harris, Jennifer R ; Scheike, Thomas ; Holst, Klaus ; Halekoh, Ulrich ; Adami, Hans-Olov ; Czene, Kamila ; Christensen, Kaare ; Holm, Niels V ; Pukkala, Eero ; Skytthe, Axel ; Kaprio, Jaakko ; Hjelmborg, Jacob B. / The Heritability of Breast Cancer among women in the Nordic Twin Study of Cancer. In: Cancer Epidemiology, Biomarkers & Prevention. 2016 ; Vol. 25, No. 1. pp. 145-50.
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title = "The Heritability of Breast Cancer among women in the Nordic Twin Study of Cancer",
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, while 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{\%} CI 10{\%} - 51{\%}) and the common environmental component was 16{\%} (95{\%} CI 10{\%} - 32{\%}). For pre-menopausal 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 post-menopausal breast cancer Impact We estimate heritability of breast cancer, taking until now ignored sources of bias into account.",
author = "S{\"o}ren M{\"o}ller and Mucci, {Lorelei A} and Harris, {Jennifer R} and Thomas Scheike and Klaus Holst and Ulrich Halekoh and Hans-Olov Adami and Kamila Czene and Kaare Christensen and Holm, {Niels V} and Eero Pukkala and Axel Skytthe and Jaakko Kaprio and Hjelmborg, {Jacob B}",
note = "Copyright {\circledC} 2015, American Association for Cancer Research.",
year = "2016",
month = "1",
doi = "10.1158/1055-9965.EPI-15-0913",
language = "English",
volume = "25",
pages = "145--50",
journal = "Cancer Epidemiology, Biomarkers & Prevention",
issn = "1055-9965",
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The Heritability of Breast Cancer among women in the Nordic Twin Study of Cancer. / Möller, Sören; Mucci, Lorelei A; Harris, Jennifer R; Scheike, Thomas; Holst, Klaus; Halekoh, Ulrich; Adami, Hans-Olov; Czene, Kamila; Christensen, Kaare; Holm, Niels V; Pukkala, Eero; Skytthe, Axel; Kaprio, Jaakko; Hjelmborg, Jacob B.

In: Cancer Epidemiology, Biomarkers & Prevention, Vol. 25, No. 1, 01.2016, p. 145-50.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - The Heritability of Breast Cancer among women in the Nordic Twin Study of Cancer

AU - Möller, Sören

AU - Mucci, Lorelei A

AU - Harris, Jennifer R

AU - Scheike, Thomas

AU - Holst, Klaus

AU - Halekoh, Ulrich

AU - Adami, Hans-Olov

AU - Czene, Kamila

AU - Christensen, Kaare

AU - Holm, Niels V

AU - Pukkala, Eero

AU - Skytthe, Axel

AU - Kaprio, Jaakko

AU - Hjelmborg, Jacob B

N1 - Copyright © 2015, American Association for Cancer Research.

PY - 2016/1

Y1 - 2016/1

N2 - 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, while 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% CI 10% - 51%) and the common environmental component was 16% (95% CI 10% - 32%). For pre-menopausal 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 post-menopausal breast cancer Impact We estimate heritability of breast cancer, taking until now ignored sources of bias into account.

AB - 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, while 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% CI 10% - 51%) and the common environmental component was 16% (95% CI 10% - 32%). For pre-menopausal 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 post-menopausal breast cancer Impact We estimate heritability of breast cancer, taking until now ignored sources of bias into account.

U2 - 10.1158/1055-9965.EPI-15-0913

DO - 10.1158/1055-9965.EPI-15-0913

M3 - Journal article

VL - 25

SP - 145

EP - 150

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 1

ER -