Blood DNA methylation signatures are associated with social determinants of health among survivors of childhood cancer

ABSTRACT

Social epigenomics is an emerging field in which social scientist collaborate with computational biologists, especially epigeneticists, to address the underlying pathway for biological embedding of life experiences. This social epigenomics study included long-term childhood cancer survivors enrolled in the St. Jude Lifetime Cohort. DNA methylation (DNAm) data were generated using the Illumina EPIC BeadChip, and three social determinants of health (SDOH) factors were assessed: self-reported educational attainment, personal income, and an area deprivation index based on census track data. An epigenome-wide association study (EWAS) was performed to evaluate the relation between DNAm at each 5’-cytosine-phosphate-guanine-3’ (CpG) site and each SDOH factor based on multivariable linear regression models stratified by ancestry (European ancestry, n = 1,618; African ancestry, n = 258). EWAS among survivors of European ancestry identified 130 epigenome-wide significant SDOH–CpG associations (P < 9 × 10⁻⁸), 25 of which were validated in survivors of African ancestry (P < 0.05). Thirteen CpGs were associated with all three SDOH factors and resided at pleiotropic loci in cigarette smoking–related genes (e.g., CLDND1 and CPOX). After accounting for smoking and body mass index, these associations remained significant with attenuated effect sizes. Seven of 13 CpGs were associated with gene expression level based on 57 subsamples with blood RNA sequencing data available. In conclusion, DNAm signatures, many resembling the effect of tobacco use, were associated with SDOH factors among survivors of childhood cancer, thereby suggesting that biologically distal SDOH factors influence health behaviours or related factors, the epigenome, and subsequently survivors’ health.

KEYWORDS:

• DNA methylation
• social determinants of health
• childhood cancer
• survivorship
• epigenome-wide association study

Acknowledgments

The authors acknowledge Dr. Angela McArthur, Department of Scientific Editing, St. Jude Children’s Research Hospital for her scientific editing.

Disclosure statement

The authors declare no potential conflicts of interest.

Authorship contributions

Z.W. and I-C.H. designed and performed the research. N.S., J-A.S., Q.D., Z.L., Y.Z., L.H., C-W.H., H.P., C.L.W., K.K.N., K.R.K., D.K.S., Y.Y., M.M.H., L.L.R., I-C.H., and Z.W. collected, analyzed, and interpreted data. N.S., J-A.S., Q.D., Z.L. Y.Z., L.H., C-W.H., H.P., C.L.W., K.K.N., K.R.K., Y.Y., M.M.H., L.L.R., I-C.H., and Z.W. performed the statistical analyses. N.S., J-A.S., I-C.H., and Z.W. wrote the manuscript. M.M.H., L.L.R., I-C.H., and Z.W. contributed administrative, technical, or material support. Z.W. and I-C.H supervised all aspects of the study.

Statement of prior presentation

Part of this work was preprinted in medRxiv (10.1101/2020.10.30.20223313) and presented in abstract from at the AACR Annual Meeting 2021, which was virtual.

Supplementary Material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by funding from the V Foundation [Grant # DT2020-014], the National Institutes of Health [Grant # CA021765, CA195547], and the American Lebanese Syrian Associated Charities (ALSAC). The funders of the study had no role in the design or conduct of the study; nor were they not involved in collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health.