Persistent variations of blood DNA methylation associated with treatment exposures and risk for cardiometabolic outcomes in long-term survivors of childhood cancer in the St. Jude Lifetime Cohort

Autor: Nan Song, Chia-Wei Hsu, Haitao Pan, Yinan Zheng, Lifang Hou, Jin-ah Sim, Zhenghong Li, Heather Mulder, John Easton, Emily Walker, Geoffrey Neale, Carmen L. Wilson, Kirsten K. Ness, Kevin R. Krull, Deo Kumar Srivastava, Yutaka Yasui, Jinghui Zhang, Melissa M. Hudson, Leslie L. Robison, I-Chan Huang, Zhaoming Wang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Genome Medicine, Vol 13, Iss 1, Pp 1-13 (2021)
Druh dokumentu: article
ISSN: 1756-994X
DOI: 10.1186/s13073-021-00875-1
Popis: Abstract Background It is well-established that cancer treatment substantially increases the risk of long-term adverse health outcomes among childhood cancer survivors. However, there is limited research on the underlying mechanisms. To elucidate the pathophysiology and a possible causal pathway from treatment exposures to cardiometabolic conditions, we conducted epigenome-wide association studies (EWAS) to identify the DNA methylation (DNAm) sites associated with cancer treatment exposures and examined whether treatment-associated DNAm sites mediate associations between specific treatments and cardiometabolic conditions. Methods We included 2052 survivors (median age 33.7 years) of European ancestry from the St. Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Cumulative doses of chemotherapy and region-specific radiation were abstracted from medical records. Seven cardiometabolic conditions were clinically assessed. DNAm profile was measured using MethylationEPIC BeadChip with blood-derived DNA. Results By performing multiple treatment-specific EWAS, we identified 935 5′-cytosine-phosphate-guanine-3′ (CpG) sites mapped to 538 genes/regions associated with one or more cancer treatments at the epigenome-wide significance level (p
Databáze: Directory of Open Access Journals
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