Medical risk factors and late effects of childhood cancer - Etiological and methodological considerations

Abstract

Many risk factors for childhood and second primary neoplasms originate from the medical field. However, most previously conducted studies showed small sample sizes and inadequate exposure assessments. The present dissertation therefore aims to improve the knowledge on medical risk factors for childhood and second primary cancers. A meta-analysis on the influence of vaccinations on childhood cancer development revealed four inverse associations between vaccinations and leukemia risk. The transcriptomic radiation-response was examined using experimental data from former childhood cancer patients and cancer-free controls from the KiKme study. In irradiation experiments, 4 hours were revealed as the time point with most differentially expressed genes in participants’ skin biopsies. The analysis of these genes showed alteration of metabolic pathways that may implicate cellular senescence. To identify effects of radiation beyond the molecular level, medical exposure during cancer therapy was evaluated by collecting information via validated questionnaires. Exposure to chemotherapeutics was associated with thyroid diseases and lipid metabolism disorders. Finally, the KiKme participants were used to examine late effects of cancer and lifestyle differences. Survivors were more affected by diseases and took more medication than controls. Survivors had a healthier lifestyle compared to controls; however, they exercised less. This dissertation contributes to the knowledge of childhood and second primary cancer development by showing that the risk for cancer development as well as for the occurrence of late adverse effects, can be influenced by medical factors. Overall, these results provide a basis for further elaboration on childhood cancers and its late effects and thus may contribute to a long-term reduction in the burden of the disease by providing options for individualized planning of therapies and identification of individuals in need of more extensive follow-up care.