학술논문
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
Document Type
article
Author
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
Source
Genome Medicine, Vol 13, Iss 1, Pp 1-13 (2021)
Subject
Language
English
ISSN
1756-994X
Abstract
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