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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
Article number3023
JournalCancers
Volume13
Issue number12
Number of pages12
ISSN2072-6694
DOIs
Publication statusPublished - 2. Jun 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Biometric modelling
  • Cumulative risk
  • Familial risk
  • Hematologic malignancy
  • Heritability
  • Risk between different cancers
  • Twin study

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