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Background <p>Individuals with Down syndrome have an elevated risk of childhood leukaemia and are suggested to have a reduced risk of solid tumours in adulthood. However, it remains unclear which cancer subtypes contribute to this pattern and the lifetime cancer risk.</p> Methods <p>This Swedish population-based matched cohort study investigated age- and subtype-specific cancer risks in Down syndrome. National healthcare registers were used to include 9742 individuals with Down syndrome, born in Sweden between 1930–2017. Each individual was matched by birth year, sex, and birth county to 50 comparisons. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazard models.</p> Results <p>Children with Down syndrome had a 20-fold increased risk of acute lymphoblastic leukaemia (ALL), and nearly a 500-fold increased risk of acute myeloid leukaemia (AML) before the age of 5. In contrast, individuals with Down syndrome had an overall lower risk of solid tumours, with significantly decreased risks for breast, prostate, lung, colorectal, gynaecological cancers, and melanoma, in adults. However, an increased risk was observed for testicular cancer and chondrosarcoma/chondroblastoma.</p> Conclusion <p>We present the most comprehensive profile of cancer risk in Down syndrome, aiming to guide clinical practices, encourage tailored surveillance recommendations, and incite research on chromosome 21’s role in oncogenesis.</p>

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Lifetime risk of solid tumors and leukemia in Down Syndrome: a population-based Swedish matched cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月26日

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  • Alexandra Wachtmeister,
  • Benedicte Bang,
  • Ida Nordgren,
  • Anna Martling,
  • Bertil Johansson,
  • Yunxia Lu,
  • Anna Skarin Nordenvall,
  • Giorgio Tettamanti,
  • Ann Nordgren

摘要

Background

Individuals with Down syndrome have an elevated risk of childhood leukaemia and are suggested to have a reduced risk of solid tumours in adulthood. However, it remains unclear which cancer subtypes contribute to this pattern and the lifetime cancer risk.

Methods

This Swedish population-based matched cohort study investigated age- and subtype-specific cancer risks in Down syndrome. National healthcare registers were used to include 9742 individuals with Down syndrome, born in Sweden between 1930–2017. Each individual was matched by birth year, sex, and birth county to 50 comparisons. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazard models.

Results

Children with Down syndrome had a 20-fold increased risk of acute lymphoblastic leukaemia (ALL), and nearly a 500-fold increased risk of acute myeloid leukaemia (AML) before the age of 5. In contrast, individuals with Down syndrome had an overall lower risk of solid tumours, with significantly decreased risks for breast, prostate, lung, colorectal, gynaecological cancers, and melanoma, in adults. However, an increased risk was observed for testicular cancer and chondrosarcoma/chondroblastoma.

Conclusion

We present the most comprehensive profile of cancer risk in Down syndrome, aiming to guide clinical practices, encourage tailored surveillance recommendations, and incite research on chromosome 21’s role in oncogenesis.