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Epidemiology

Neoplasm risk in individuals with neurofibromatosis 1 – a Danish nationwide cohort study with long-term follow-up

British Journal of Cancer volume 134, pages 618–626 (2026) Cite this article

Subjects

Abstract

Background

As larger population-based studies assessing neoplasm risk in neurofibromatosis 1 (NF1) are limited, we aimed to evaluate overall neoplasm risk, specific cancer types, and second primary cancers.

Methods

Using Danish registries and clinical databases, we identified 2053 individuals with NF1 and 20,530 population comparisons. We calculated cumulative incidences for first and second primary neoplasms for the study population born 1971–2020 and for adult-onset cancers in the study population born 1951–2020. We used multistate models to estimate the probabilities of being neoplasm-free, having one neoplasm, having ≥two neoplasms or being dead at a certain age.

Results

The 50-year cumulative incidence of any first neoplasm was 27.2% (95% confidence interval [CI] 23.1–31.4%) for NF1 individuals and 5.0% (4.0–6.0%) for comparisons. Moreover, the cumulative incidence of second primary neoplasm was 21.1% (14.4–27.8%) for NF1 individuals and 6.4% (0.0–15.0%) for comparisons 20 years after the first neoplasm. A person born with NF1 had a 69.8% (65.6–74.2%) probability of being alive and without neoplasm history at age 50 compared to 93.5% (92.4–94.6%) for a person without NF1.

Conclusion

The highly increased risks for primary and secondary neoplasms and mortality warrant close clinical surveillance of individuals with NF1.

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Fig. 1: Cumulative risks with 95% confidence intervals of the first neoplasm at age 0–50 years.
The alternative text for this image may have been generated using AI.
Fig. 2: Cumulative risks with 95% confidence intervals of adult-onset cancers at age 0–70 years.
The alternative text for this image may have been generated using AI.
Fig. 3: Predicted probabilities for being alive and without a neoplasm history, being alive and having one neoplasm diagnosis, being alive and having two or more neoplasm diagnoses, and being dead at age 0–50 years for the 1971–2020 study population with NF1 and matched comparisons.
The alternative text for this image may have been generated using AI.

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Data availability

Data handling and analyses were performed through the Danish Cancer Institute’s secure server at Statistics Denmark. The authors do not have permission to share the data, but researchers who fulfil the Danish legal requirements for accessing personal sensitive data can apply for access.

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Acknowledgements

We would like to thank the Danish Clinical Quality Program – National Clinical Registries (RKKP) for their help in providing data for this publication (RAREDIS).

Funding

This work was supported by the Novo Nordisk Foundation (grant number NF20OC0064537).

Author information

Authors and Affiliations

  1. Childhood Cancer Research Group, Danish Cancer Institute, Copenhagen, Denmark

    Mia Aagaard Doherty, Anja Krøyer, Thomas T. Nielsen & Line Kenborg

  2. Statistics and Data Analysis, Danish Cancer Institute, Copenhagen, Denmark

    Kathrine Grell

  3. Centre for Rare Diseases, Dept. of Paediatrics and Adolescent Medicine, Rigshospitalet. Copenhagen University Hospital, Copenhagen, Denmark

    Hanne Hove

  4. Centre for Rare Diseases, Dept. of Paediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

    Mette M. Handrup, John R. Østergaard & Cecilie Ejerskov

  5. Haematology Research Group, Danish Cancer Institute, Copenhagen, Denmark

    Henrik Hjalgrim

  6. Department of Paediatrics, University of Oklahoma, Oklahoma City, OK, USA

    John J. Mulvihill

  7. Cancer Epidemiology and Surveillance, Danish Cancer Institute, Copenhagen, Denmark

    Jan Wohlfahrt

  8. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    Jan Wohlfahrt

  9. Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

    Henrik Hasle

Authors
  1. Mia Aagaard Doherty
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Contributions

MAD took part in the conceptualisation, data curation, formal analysis, investigation, methodology, project administration, validation, visualisation, and writing of both the original draft and review and editing. KG took part in the conceptualisation, data curation, formal analysis, investigation, methodology, validation and visualisation. AK and TTN took part in data curation, investigation, validation, and resources. LK took part in conceptualisation, data curation, funding acquisition, formal analysis, methodology, supervision, validation, and visualisation. JW took part in conceptualisation, formal analysis, methodology and visualisation. CE, H Hove, and MMH contributed to conceptualisation, funding acquisition, formal analysis, and methodology. H. Hasle and H. Hjalgrim took part in the formal analysis and methodology. JJM and JRØ contributed to the formal analysis and funding acquisition. All authors took part in the writing – review and editing.

Corresponding author

Correspondence to Mia Aagaard Doherty.

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Competing interests

The authors declare no competing interests.

Ethics approval

Following the General Data Protection Regulation, the study is registered in the Danish Cancer Institute’s local archive (record number 2019-DCRC-0063). According to Danish regulations, ethics approval and informed consent are not required for studies using only register data.

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Doherty, M.A., Grell, K., Hove, H. et al. Neoplasm risk in individuals with neurofibromatosis 1 – a Danish nationwide cohort study with long-term follow-up. Br J Cancer 134, 618–626 (2026). https://doi.org/10.1038/s41416-025-03316-7

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