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Series GSE169156 Query DataSets for GSE169156
Status Public on Mar 19, 2021
Title Persistent Variations of Blood DNA Methylation Associated with Treatment Exposures and Risk for Cardiometabolic Outcomes in Childhood Cancer Survivors
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Background: It is well-established that cancer treatment substantially increases 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 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 2,052 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 epigenome-wide significance level (P<9×10-8). Among the treatment-associated CpGs, 8 were associated with obesity, 63 with hypercholesterolemia, and 17 with hypertriglyceridemia (False-Discovery-Rate-Adjusted P<0.05). We observed substantial mediation by methylation at four independent CpGs (cg06963130, cg21922478, cg22976567, cg07403981) for association between abdominal field radiotherapy (abdominal-RT) and risk of hypercholesterolemia (70.3%) and by methylation at three CpGs (cg19634849, cg13552692, cg09853238) for association between abdominal-RT and hypertriglyceridemia (54.6%). In addition, three CpGs (cg26572901, cg12715065, cg21163477) partially mediated the association between brain-RT and obesity with 32.9% mediation effect and two CpGs mediated the association between corticosteroids and obesity (cg22351187, 14.2%) and between brain-RT and hypertriglyceridemia (cg13360224, 10.5%). Notably, several mediator CpGs reside in the proximity of well-established dyslipidemia genes: cg21922478 (ITGA1) and cg22976567 (LMNA).
Conclusions: In childhood cancer survivors, cancer treatment exposures are associated with DNAm patterns present decades following the exposure. Treatment-associated DNAm sites may mediate the causal pathway from specific treatment exposures to certain cardiometabolic conditions, suggesting the utility of DNAm sites as risk predictors and potential mechanistic targets for future intervention studies.
 
Overall design We included 2,052 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.
 
Contributor(s) Song N, Wang Z, Hsu C, Pan H, Zheng Y, Hou L, Sim J, Li Z, Mulder H, Easton J, Walker E, Neale G, Wilson CL, Ness KK, Krull KR, Srivastava DK, Yasui Y, Zhang J, Hudson MM, Robison LL, Huang I
Citation(s) 33823916, 35313970, 36256508
Submission date Mar 18, 2021
Last update date Jun 01, 2023
Contact name Zhaoming Wang
E-mail(s) zhaoming.wang@stjude.org
Phone (901) 595-0232
Organization name St. Jude Children's Research Hospital
Department Epidemiology & Cancer Control
Street address 262 Danny Thomas Place
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL23976 Illumina Infinium HumanMethylation850 BeadChip
Samples (2052)
GSM5177045 genomic DNA derived from blood samples from survivor of childhood cancer [SJNHL017924_G1]
GSM5177046 genomic DNA derived from blood samples from survivor of childhood cancer [SJSTS018869_G1]
GSM5177047 genomic DNA derived from blood samples from survivor of childhood cancer [SJALL018469_G1]
Relations
BioProject PRJNA715452

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE169156_RAW.tar 28.5 Gb (http)(custom) TAR (of IDAT)
GSE169156_SJLIFE_IlluminaEPIC_2052samples_GEO_03162021_processed.txt.gz 6.7 Gb (ftp)(http) TXT
GSE169156_SJLIFE_IlluminaEPIC_2052samples_GEO_03162021_signal.txt.gz 14.6 Gb (ftp)(http) TXT
Processed data are available on Series record
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