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

## TL;DR

People with Down syndrome have a much higher risk of childhood leukemia but lower risks of many adult cancers, according to a large Swedish study.

## Contribution

This study provides the most detailed lifetime cancer risk profile for individuals with Down syndrome using a large population-based cohort.

## Key findings

- Children with Down syndrome had a 20-fold increased risk of ALL and nearly 500-fold increased risk of AML before age 5.
- Individuals with Down syndrome had significantly reduced risks of breast, prostate, lung, colorectal, gynaecological cancers, and melanoma in adulthood.
- Higher risks were observed for testicular cancer and chondrosarcoma/chondroblastoma in individuals with Down syndrome.

## Abstract

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.

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.

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.

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.