Vulnerability and Protection: Integrative Literature Review on the Contrasting Risk of Leukemias and Solid Tumors in Down Syndrome
DOI:
https://doi.org/10.32635/2176-9745.RBC.2026v72n1.5334Keywords:
Down syndrome/complications, Leukemia/epidemiology, Neoplasms/genetics, Genetic Predisposition to DiseaseAbstract
Introduction: Down syndrome (DS), characterized by trisomy of chromosome 21, is associated with an increased risk of leukemia and a reduced incidence of solid tumors. Objective: To analyze the epidemiological patterns and molecular mechanisms that explain the increased susceptibility to leukemias and protection against solid neoplasms in individuals with DS. Method: Seventeen studies with different designs were selected, totaling 62,121 individuals. Result: The overall prevalence of cancer was 2.02%, with 1.18% of leukemias (predominantly AML and ALL) and 0.22% of solid tumors (testicular cancer being the most common). The standardized incidence ratio (SIR) was low for solid tumors (0.69), with especially low values for lung (0.10), skin (0.24), and breast (0.35). In contrast, there was an increased risk of testicular (SIR: 4.28) and liver (SIR: 3.72) cancer. From a molecular point of view, the GATA1 mutation was found in virtually all cases of AML in DS, while increased expression of tumor suppressor genes, such as RCAN1 and DYRK1A, may explain the lower incidence of solid tumors in this population. Conclusion: It is concluded that DS presents a unique oncological profile, with a specific predisposition to leukemias in childhood and protection against solid neoplasms, especially in adulthood.
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