Joanna Sulicka-Grodzicka1, Andrzej Surdacki2, Michał Seweryn3,4, Tomasz Mikołajczyk5, Krzysztof Rewiuk6, Tomasz Guzik5, Tomasz Grodzicki6. 1. Department of Rheumatology, Jagiellonian University Medical College, Krakow, Poland. 2. 2nd Department of Cardiology, Jagiellonian University Medical College, Krakow, Poland. 3. Center for Medical Genomics, OMICRON, Jagiellonian University Medical College, Krakow, Poland. 4. Department of Cancer Biology and Genetics, Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus, OH, USA. 5. Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland. 6. Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow, Poland.
Abstract
BACKGROUND: The long-term consequences of chemotherapy and radiotherapy result in a high prevalence and early onset of age-related chronic diseases in survivors. We aimed to examine whether childhood and adolescent cancer survivors (CS) demonstrate biomarkers of accelerated aging. METHODS: We evaluated 50 young adult CS at 11 [8-15] years after cancer diagnosis, and 30 healthy, age and sex-matched controls, who were unexposed to cancer therapy. Using a machine-learning approach, we assessed factors discriminating CS from controls and compared selected biomarkers and lymphocyte subpopulations with data from the Framingham Heart Study (FHS) cohort and the Genotype Tissue Expression (GTEx) project. RESULTS: Survivors compared with controls had higher levels of C-reactive protein and fibrinogen. The surface expression of CD38 on T cells was increased, and there was an increase in the percentage of memory T cells in survivors, compared with the unexposed group. The relationships between above cell subpopulations and age were consistent in CS, FHS, and GTEx cohorts, but not in controls. CONCLUSIONS: Young pediatric cancer survivors differ from age-related controls in terms of activation of the adaptive immune system and chronic, low-grade inflammation. These changes resemble aging phenotype observed in older population. Further research in biomarkers of aging in young, adult childhood cancer survivors is warranted, as it may facilitate screening and prevention of comorbidities in this population.
BACKGROUND: The long-term consequences of chemotherapy and radiotherapy result in a high prevalence and early onset of age-related chronic diseases in survivors. We aimed to examine whether childhood and adolescent cancer survivors (CS) demonstrate biomarkers of accelerated aging. METHODS: We evaluated 50 young adult CS at 11 [8-15] years after cancer diagnosis, and 30 healthy, age and sex-matched controls, who were unexposed to cancer therapy. Using a machine-learning approach, we assessed factors discriminating CS from controls and compared selected biomarkers and lymphocyte subpopulations with data from the Framingham Heart Study (FHS) cohort and the Genotype Tissue Expression (GTEx) project. RESULTS: Survivors compared with controls had higher levels of C-reactive protein and fibrinogen. The surface expression of CD38 on T cells was increased, and there was an increase in the percentage of memory T cells in survivors, compared with the unexposed group. The relationships between above cell subpopulations and age were consistent in CS, FHS, and GTEx cohorts, but not in controls. CONCLUSIONS: Young pediatric cancer survivors differ from age-related controls in terms of activation of the adaptive immune system and chronic, low-grade inflammation. These changes resemble aging phenotype observed in older population. Further research in biomarkers of aging in young, adult childhood cancer survivors is warranted, as it may facilitate screening and prevention of comorbidities in this population.
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