A unique cancer risk profile in Down Syndrome: Higher leukemia risk in childhood
Children with Down syndrome have a significantly increased risk of leukemia, while adults have a lower risk of several common solid tumors, according to a new register study from Karolinska Institutet published in the British Journal of Cancer. The results may contribute to more tailored cancer screening guidelines.
In a large, Swedish population-based register study, the risk of different cancer types in individuals with Down syndrome was mapped across the lifespan. The results show a markedly increased risk of leukemia during childhood, with a nearly 500-fold increased risk of acute myeloid leukemia (AML) before age 5, and a 20-fold increased risk of acute lymphoblastic leukemia (ALL). Despite this, only 2.5 per cent of all individuals with Down syndrome developed leukemia during childhood.
In adulthood, however, a clearly reduced risk was observed for most solid tumors, including breast, prostate, lung, colorectal, and gynecological cancers, as well as melanoma. Although the study showed an overall lower cancer risk in adults, there was an increased risk of testicular cancer, as well as new associations between Down syndrome and certain rare forms of bone cancer.
“Our results shows the very high risk of leukemia early in life, but at the same time show that the majority of children with Down syndrome never develop cancer,” says Ann Nordgren, adjunct professor of clinical genetics at the Department of Molecular Medicine and Surgery, Karolinska Institutet, who led the study.
“The results may pave the way for more precise and individualised cancer screening guidelines, helping clinicians, families, and policymakers to provide appropriate care and follow‑up where certain screening procedures could likely be modified, such as the choice of method for breast cancer screening, while others may need to be introduced, such as targeted testicular examinations.”
“The findings also suggest that trisomy 21 may have a protective effect against several types of solid tumors. This opens new opportunities for in-depth research into cancer-suppressive mechanisms. The results may have important clinical implications, not only for individuals with Down syndrome, but also for the broader population.”
The study included nearly 10,000 individuals with Down syndrome born between 1930 and 2017. Individuals were identified by linking data from several national registers, including the National Patient Register, the Medical Birth Register, the Cancer Register, the Swedish Childhood Cancer Register, as well as genetic data from Swedish university laboratories. Each individual was matched to 50 comparisons of the same sex, birth year, and county of birth. The cohorts were then followed over time to study the incidence of different cancer types.
“Future work includes developing consensus cancer screening guidelines specifically tailored for individuals with Down syndrome. Next steps also include further biological studies to confirm and understand how and why chromosome 21 appears to protect against solid tumors - knowledge that is not only relevant for individuals with Down syndrome but also valuable for cancer research as a whole,” says Ann Nordgren.
The study was funded by the Swedish Childhood Cancer Fund, the Swedish Research Council, the Swedish Cancer Society, the Stockholm Cancer Society, the Foundation of the Freemasons’ Children’s House in Stockholm, the Bertil Hållsten Research Foundation, the Berth von Kantzow Foundation, and Region Stockholm.
Publication
"Lifetime risk of solid tumors and leukemia in Down Syndrome: a population-based Swedish matched cohort study", Alexandra Wachtmeister, Benedicte Bang, Ida Nordgren, Anna Martling, Bertil Johansson, Yunxia Lu, Anna Skarin Nordenvall, Giorgio Tettamanti, Ann Nordgren. British Journal of Cancer, online 26 December 2025, doi: 10.1038/s41416-025-03318-5.