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Article

Familial Risk and Heritability of Hematologic Malignancies in the Nordic Twin Study of Cancer

1
Department of Epidemiology, Biostatistics, and Biodemography, Institute of Public Health, University of Southern Denmark, 5000 Odense C, Denmark
2
Danish Twin Registry, Institute of Public Health, University of Southern Denmark, 5000 Odense C, Denmark
3
Division of Health Data and Digitalisation, Norwegian Institute of Public Health, 0213 Oslo, Norway
4
Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark
5
Department of Statistics, Paraná Federal University, Curitiba 81531-980, Brazil
6
Department of Haematology, Odense University Hospital, 5000 Odense C, Denmark
7
Department of Clinical Research, Institute of Public Health, University of Southern Denmark, 5000 Odense C, Denmark
8
Department of Public Health and Institute for Molecular Medicine Finland, University of Helsinki, 00014 Helsinki, Finland
*
Author to whom correspondence should be addressed.
Academic Editor: Francesco Bertolini
Cancers 2021, 13(12), 3023; https://doi.org/10.3390/cancers13123023
Received: 12 May 2021 / Revised: 11 June 2021 / Accepted: 11 June 2021 / Published: 16 June 2021
(This article belongs to the Special Issue Familial Cancer and Germline Genetics)
Hematologic malignancies account for 8–9% of all incident cancers. Both genetic and environmental risk factors contribute to cancer development, but it is unclear if there is shared heritability between hematologic malignancies. This study aimed to investigate familial predisposition to hematologic malignancies using the largest twin study of cancer in the world. We compared individual risk in the general population and the risk of cancer in one twin before some age given that the other twin had (another) cancer before that age. Furthermore, by analyzing information about whether the twins were identical or fraternal, we could estimate the relative importance of genetic and environmental influences on the risk for developing hematologic cancers. This study confirmed previous findings of familial predisposition to hematologic malignancies and provides novel evidence that familial predisposition decreases with increasing age. The latter points to the importance of taking age into account in the surveillance of hematological cancers.
We aimed to explore the genetic and environmental contributions to variation in the risk of hematologic malignancies and characterize familial dependence within and across hematologic malignancies. The study base included 316,397 individual twins from the Nordic Twin Study of Cancer with a median of 41 years of follow-up: 88,618 (28%) of the twins were monozygotic, and 3459 hematologic malignancies were reported. We estimated the cumulative incidence by age, familial risk, and genetic and environmental variance components of hematologic malignancies accounting for competing risk of death. The lifetime risk of any hematologic malignancy was 2.5% (95% CI 2.4–2.6%), as in the background population. This risk was elevated to 4.5% (95% CI 3.1–6.5%) conditional on hematologic malignancy in a dizygotic co-twin and was even greater at 7.6% (95% CI 4.8–11.8%) if a monozygotic co-twin had a hematologic malignancy. Heritability of the liability to develop any hematologic malignancy was 24% (95% CI 14–33%). This estimate decreased across age, from approximately 55% at age 40 to about 20–25% after age 55, when it seems to stabilize. In this largest ever studied twin cohort with the longest follow-up, we found evidence for familial risk of hematologic malignancies. The discovery of decreasing familial predisposition with increasing age underscores the importance of cancer surveillance in families with hematological malignancies. View Full-Text
Keywords: twin study; cumulative risk; familial risk; risk between different cancers; heritability; biometric modelling; hematologic malignancy twin study; cumulative risk; familial risk; risk between different cancers; heritability; biometric modelling; hematologic malignancy
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MDPI and ACS Style

Clemmensen, S.B.; Harris, J.R.; Mengel-From, J.; Bonat, W.H.; Frederiksen, H.; Kaprio, J.; Hjelmborg, J.v.B. Familial Risk and Heritability of Hematologic Malignancies in the Nordic Twin Study of Cancer. Cancers 2021, 13, 3023. https://doi.org/10.3390/cancers13123023

AMA Style

Clemmensen SB, Harris JR, Mengel-From J, Bonat WH, Frederiksen H, Kaprio J, Hjelmborg JvB. Familial Risk and Heritability of Hematologic Malignancies in the Nordic Twin Study of Cancer. Cancers. 2021; 13(12):3023. https://doi.org/10.3390/cancers13123023

Chicago/Turabian Style

Clemmensen, Signe B., Jennifer R. Harris, Jonas Mengel-From, Wagner H. Bonat, Henrik Frederiksen, Jaakko Kaprio, and Jacob v.B. Hjelmborg 2021. "Familial Risk and Heritability of Hematologic Malignancies in the Nordic Twin Study of Cancer" Cancers 13, no. 12: 3023. https://doi.org/10.3390/cancers13123023

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