Social Genomic Mechanisms of Health Disparities Among Adolescent/Young Adult Survivors of Hodgkin and Non-Hodgkin Lymphoma: ECOG-ACRIN E

Research in human social genomics maps molecular pathways through which social and psychological factors regulate gene expression in immune cells and tumor tissue, thus affecting chronic disease progression, symptom development, antiviral resistance, morbidity, and mortality. In many cases, psychosocial factors trigger neural and endocrine responses that regulate expression of genes involved in cancer progression (inflammation, metastasis, and treatment resistance) and immune function (stimulating inflammatory genes and suppressing antiviral gene transcription, as observed in the “Conserved Transcriptional Response to Adversity”/CTRA transcriptome signature). However, nothing is known about how such effects impact Adolescent and Young Adult (AYA) cancer survivors. This study aims to identify functional genomic pathways through which psychosocial factors influence gene regulation and alter health outcomes in AYA cancer patients; and define the role of such effects in structuring health disparities in post-treatment survivorship.

This longitudinal prospective single-cohort study is administered through the ECOG-ACRIN Cancer Research Group and activated in 2023. Subjects are currently being accrued through the NCI Community Oncology Research Program and via self-referral through a broad network of cancer support organizations and clinical programs that serve the AYA population. Eligibility includes survivors of Hodgkin or Non-Hodgkin Lymphoma or acute lymphocytic leukemia who have achieved complete response to therapy at time of study registration; were aged 15–39 years at time of diagnosis; and recruited within 3 years following completion of treatment.

Upon enrollment, participants complete an online survey of patient-reported outcome measures of social and psychological risk and resilience factors, including quality of life (QOL), social isolation, socioeconomic status, experiences of racism and discrimination, and exposures to childhood trauma. Clinical records are reviewed for medically reported comorbidities and vital status. Data are collected at baseline and repeated every 6 months for 2 years.

Blood specimens also are collected at each time point. The CTRA transcriptome profile will be assayed using an established 53-gene index comprised of a block of 19 pro-inflammatory genes (e.g., IL1B, IL6, IL8/CXCL8, TNF) and 34 genes involved in innate antiviral response (e.g., IFNA/B, IFI-, OAS-, and MX-family genes), with CTRA representing the difference in average expression of those 2 blocks (inflammatory—interferon). CTRA is a biological intermediate state, which is hypothesized to mediate relationships between proposed psychosocial risk and resilience factors and outcomes (morbidity, mortality, and QOL).

Defining effects of psychosocial conditions on gene expression and their role in structuring disparities for AYA survivors will fill a critical gap in knowledge that informs risk-based models for cancer survivorship care. This study will be significant in that it will inform the conceptualization and development of targeted medical and supportive care interventions that reduce risks for morbidity and mortality and improve the QOL for AYAs.