Familial risk and heritability of hematologic malignancies in the nordic twin study of cancer

Signe B. Clemmensen*, Jennifer R. Harris, Jonas Mengel-From, Wagner H. Bonat, Henrik Frederiksen, Jaakko Kaprio, Jacob V.B. Hjelmborg

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Abstrakt

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.

OriginalsprogEngelsk
Artikelnummer3023
TidsskriftCancers
Vol/bind13
Udgave nummer12
Antal sider12
ISSN2072-6694
DOI
StatusUdgivet - 2. jun. 2021

Bibliografisk note

Funding Information:
Funding: This research was funded by grants from the Nordic Cancer Union grant number 195020, project entitled “Genetic Epidemiology and Familial Risk of Cross-Cancer Associations: A Nordic Twin Study-II”, and from the AgeCare program of the Academy of Geriatric Cancer Research, Odense University Hospital, as well as by a scholarship from the Faculty of Health Sciences, University of Southern Denmark.

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