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
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.
UR - http://www.ncbi.nlm.nih.gov/pubmed/26554920
UR - http://www.mendeley.com/research/heritability-breast-cancer-among-women-nordic-twin-study-cancer
U2 - 10.1158/1055-9965.epi-15-0913
DO - 10.1158/1055-9965.epi-15-0913
M3 - Tidsskriftartikel
C2 - 26554920
SN - 1055-9965
VL - 25
SP - 145
EP - 150
JO - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ER -