Abstract 685: A social epigenomic investigation of racial disparity in pulmonary impairment among aging survivors of childhood cancer
Authors: Song Nan , Sim Jin-ah , Dong Qian , Zheng Yinan , Hou Lifang , Li Zhenghong , Hsu Chia-Wei , Pan Haitao , Mulder Heather , Easton John , Walker Emily , Neale Geoffrey , Wilson Carmen L. , Ness Kirsten K. , Krull Kevin R. , Srivastava Deo Kumar , Yasui Yutaka , Zhang Jinghui , Hudson Melissa M. , Robison Leslie L. , Huang I-Chan , Wang Zhaoming 
Published: July 2021

Abstract
Background: Prior research suggests that social determinants of health (SDOH) may influence health through an epigenetic mechanism. However, the social epigenomic approach has not yet been applied to childhood cancer survivors, a population at high risk for chronic health conditions. We aim to investigate how SDOH factors contribute to racial disparity in pulmonary impairment with survivors from the St. Jude Lifetime Cohort Study.
Methods: DNA methylation (DNAm) profile was generated with EPIC BeadChip using blood derived DNA. SDOH factors included educational attainment and personal income self-reported using a survey, and socioeconomic area deprivation index (ADI) geocoded using full home addresses. Clinically assessed pulmonary impairment included pulmonary diffusion deficits (PDD), restrictive pulmonary deficits (RPD) and obstructive pulmonary deficits (OPD). Epigenome-wide association study (EWAS) was performed to evaluate the association between DNAm at each CpG and each SDOH factor. Mediation analysis was conducted by treating each SDOH-associated CpG as a mediator, SDOH factor as an exposure, and specific pulmonary condition as the outcome. Genetically inferred races, i.e. survivors of European ancestry (EA) and African ancestry (AA), were considered.
Results: The study included 258 AA (median time from cancer diagnosis [MTD]=25.2 years, interquartile range [IQR]=19.9-32.1 years) and 1,618 EA survivors (MTD=27.3, IQR=21.1-33.7 years). Compared to EA survivors, AA survivors had lower educational attainment (P&lt;0.0001), lower personal income (P&lt;0.0001), and higher ADI (P&lt;0.0001). Compared to EA survivors, incidence of PDD (25.2% in AA vs 18.2% in EA, P=0.03) and RPD (14.2% in AA vs 7.5% in EA, P=0.002) were significantly higher in AA survivors, whereas OPD were comparable between groups (9.8% vs 13.1%, P=0.21). However, the racial disparity in PDD became nonsignificant after adjusting for SDOH. EWAS identified 130 SDOH-CpG associations at epigenome-wide significance (P&lt;9×10-8) including 88 for educational attainment, 23 for personal income, and 19 for ADI. Thirteen CpGs, commonly associated with all three SDOH factors, resided at pleiotropic loci featuring cigarette smoking genes, e.g. CPOX and AHRR among others. Three independent SDOH-associated CpGs (cg04180924, cg1120500, and cg27470486) had a significant combined mediation effect for educational attainment (%mediation = 48.9%), and a single mediator cg08064403 had a significant mediation effect for personal income (25.9%) and ADI (24.1%) on PDD risk.
Conclusions: DNAm signatures, many resembling the effect of tobacco use, are associated with educational attainment, personal income, and ADI. Our findings suggest that these DNAm are potential mechanistic mediators for the effects of SDOH factors on PDD risk. Through this mechanism, poor SDOH factors in AA survivors led to racial disparity in PDD.
Citation Format: Nan Song, Jin-ah Sim, Qian Dong, Yinan Zheng, Lifang Hou, Zhenghong Li, Chia-Wei Hsu, Haitao Pan, 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. A social epigenomic investigation of racial disparity in pulmonary impairment among aging survivors of childhood cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 685.