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 biologic...

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Main Authors: Jianhong Chen, Mark D. Long, Sirinapa Sribenja, Sung Jun Ma, Li Yan, Qiang Hu, Song Liu, Thaer Khoury, Chi-Chen Hong, Elisa Bandera, Anurag K. Singh, Elizabeth A. Repasky, Elizabeth G. Bouchard, Michael Higgins, Christine B. Ambrosone, Song Yao
Format: Article
Language:English
Published: BMC 2023-04-01
Series:Clinical Epigenetics
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Online Access:https://doi.org/10.1186/s13148-023-01470-4
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author Jianhong Chen
Mark D. Long
Sirinapa Sribenja
Sung Jun Ma
Li Yan
Qiang Hu
Song Liu
Thaer Khoury
Chi-Chen Hong
Elisa Bandera
Anurag K. Singh
Elizabeth A. Repasky
Elizabeth G. Bouchard
Michael Higgins
Christine B. Ambrosone
Song Yao
author_facet Jianhong Chen
Mark D. Long
Sirinapa Sribenja
Sung Jun Ma
Li Yan
Qiang Hu
Song Liu
Thaer Khoury
Chi-Chen Hong
Elisa Bandera
Anurag K. Singh
Elizabeth A. Repasky
Elizabeth G. Bouchard
Michael Higgins
Christine B. Ambrosone
Song Yao
author_sort Jianhong Chen
collection DOAJ
description 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.
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spelling doaj.art-f1076641aa4049a1a139134b19728f572023-04-30T11:19:19ZengBMCClinical Epigenetics1868-70832023-04-0115111010.1186/s13148-023-01470-4An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patientsJianhong Chen0Mark D. Long1Sirinapa Sribenja2Sung Jun Ma3Li Yan4Qiang Hu5Song Liu6Thaer Khoury7Chi-Chen Hong8Elisa Bandera9Anurag K. Singh10Elizabeth A. Repasky11Elizabeth G. Bouchard12Michael Higgins13Christine B. Ambrosone14Song Yao15Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer CenterDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer CenterDepartment of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer CenterDepartment of Radiation Oncology, Roswell Park Comprehensive Cancer CenterDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer CenterDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer CenterDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer CenterDepartment of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer CenterDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer CenterCancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, The State University of New JerseyDepartment of Radiation Oncology, Roswell Park Comprehensive Cancer CenterDepartment of Immunology, Roswell Park Comprehensive Cancer CenterDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer CenterDepartment of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer CenterDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer CenterDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer CenterAbstract 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.https://doi.org/10.1186/s13148-023-01470-4DNA methylationBreast cancerSocioeconomic positionHousehold incomeNNTGPR37
spellingShingle Jianhong Chen
Mark D. Long
Sirinapa Sribenja
Sung Jun Ma
Li Yan
Qiang Hu
Song Liu
Thaer Khoury
Chi-Chen Hong
Elisa Bandera
Anurag K. Singh
Elizabeth A. Repasky
Elizabeth G. Bouchard
Michael Higgins
Christine B. Ambrosone
Song Yao
An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients
Clinical Epigenetics
DNA methylation
Breast cancer
Socioeconomic position
Household income
NNT
GPR37
title An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients
title_full An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients
title_fullStr An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients
title_full_unstemmed An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients
title_short An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients
title_sort epigenome wide analysis of socioeconomic position and tumor dna methylation in breast cancer patients
topic DNA methylation
Breast cancer
Socioeconomic position
Household income
NNT
GPR37
url https://doi.org/10.1186/s13148-023-01470-4
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