An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients

Abstract

Background Disadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP. Methods Based on tumor DNA methylation data from the Illumina 450 K array from 694 breast cancer patients in the Women’s Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income. Functional impact of the identified CpG sites was explored in silico using data from publicly available databases. Results We identified 25 CpG sites associated with household income at an array-wide significance level, but none with educational attainment. Two of the top CpG sites, cg00452016 and cg01667837, were in promoter regions of NNT and GPR37, respectively, with multiple epigenetic regulatory features identified in each region. NNT is involved in β-adrenergic stress signaling and inflammatory responses, whereas GPR37 is involved in neurological and immune responses. For both loci, gene expression was inversely correlated to the levels of DNA methylation. The associations were consistent between Black and White women and did not differ by tumor estrogen receptor (ER) status. Conclusions In a large breast cancer patient population, we discovered evidence of the significant biological impact of household income on the tumor DNA methylome, including genes in the β-adrenergic stress and immune response pathways. Our findings support biological effects of socioeconomic status on tumor tissues, which might be relevant to cancer development and progression.

Orphan G Protein-Coupled Receptor GPR37 as an Emerging Therapeutic Target

“…118,119 crucial to comprehend the role of GPR37 in peripheral cancers, as protein−protein interaction (PPI) analysis has revealed its involvement in a functional pathway that facilitates breast cancer metastasis to the brain and lungs. 120,121 Furthermore, analysis of the Cancer Genome Atlas and Oncomine databases has shown high expression of GPR37 in lung adenocarcinoma (LUAD), with upregulation associated with unfavorable outcomes. 122,123 Gain-or LOF assays have demonstrated that increased GPR37 expression enhances the activation of TGF-β1, Smad2, and Smad3 phosphorylation, leading to improved proliferation, migration, and invasion of carcinoma cells in vitro.…”

“…A multiomics pilot study using mass spectrometry on cerebrospinal fluid (CSF) from recurrent MB patients revealed the upregulation of GPR37, as well as ADAMTS1 and GAP43 indicating the presence of hypoxic conditions, in the CSF of these patients . Functional studies have demonstrated that elevated levels of GPR37 promote tumor cell proliferation, migration, and invasion, while suppressing GPR37 through knockdown techniques inhibits malignant behaviors. , GPR37 is crucial to comprehend the role of GPR37 in peripheral cancers, as protein–protein interaction (PPI) analysis has revealed its involvement in a functional pathway that facilitates breast cancer metastasis to the brain and lungs. , …”