Epigenetic Aging in Childhood Cancer Survivors

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BACKGROUND: Pediatric cancer survivors remain at risk for numerous late effects of therapy and have shown signs of advanced aging. The specific mechanisms at play are unclear but epigenetic modulation may play a role. METHODS: This cross-sectional study included 20 pediatric cancer survivors who received intensive chemotherapy with or without radiation and were a minimum of 5 years from treatment and 20 healthy biological siblings. DNA methylation patterns were analyzed from peripheral blood samples to determine epigenetic age (the difference between biological age and chronological age). Paired t test analysis or the Wilcoxon signed-rank test was used to compare results between survivors and siblings. RESULTS: The childhood cancer survivor cohort consisted of 12 males and 8 females; the comparative sibling cohort consisted of 8 males and 12 females. Mean chronological age was 15.2±6.28 years for survivors and 16.4±8.31 years for siblings (mean±SD). Survivors demonstrated increased epigenetic age compared with siblings (1.38±3.71 vs. -0.03±3.12 y (mean±SD), mean difference 1.41, [0.30 to 2.52], P=0.016, n=20 pairs). Patients who additionally received photon radiation demonstrated a more notable increase in epigenetic age compared with siblings (3.33±4.13 vs. 0.78±3.04 y (mean±SD), mean difference 2.55, [0.75 to 4.35], P=0.012, n=8 pairs). CONCLUSIONS: Childhood cancer survivors demonstrate increased epigenetic age compared with their healthy siblings. Exposure to radiation was associated with further increased epigenetic age. Epigenetic modulation through DNA methylation may be a potential mechanism contributing to the aging process in childhood cancer survivors.

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