Cargando…

Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer

A primary difference between black women (BW) and white women (WW) diagnosed with breast cancer is aggressiveness of the tumor. Black women have higher mortalities with similar incidence of breast cancer compared to other race/ethnicities, and they are diagnosed at a younger age with more advanced t...

Descripción completa

Detalles Bibliográficos
Autores principales: Rujchanarong, Denys, Scott, Danielle, Park, Yeonhee, Brown, Sean, Mehta, Anand S., Drake, Richard, Sandusky, George E., Nakshatri, Harikrishna, Angel, Peggi M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273232/
https://www.ncbi.nlm.nih.gov/pubmed/35832545
http://dx.doi.org/10.3389/fonc.2022.876651
_version_ 1784745030706003968
author Rujchanarong, Denys
Scott, Danielle
Park, Yeonhee
Brown, Sean
Mehta, Anand S.
Drake, Richard
Sandusky, George E.
Nakshatri, Harikrishna
Angel, Peggi M.
author_facet Rujchanarong, Denys
Scott, Danielle
Park, Yeonhee
Brown, Sean
Mehta, Anand S.
Drake, Richard
Sandusky, George E.
Nakshatri, Harikrishna
Angel, Peggi M.
author_sort Rujchanarong, Denys
collection PubMed
description A primary difference between black women (BW) and white women (WW) diagnosed with breast cancer is aggressiveness of the tumor. Black women have higher mortalities with similar incidence of breast cancer compared to other race/ethnicities, and they are diagnosed at a younger age with more advanced tumors with double the rate of lethal, triple negative breast cancers. One hypothesis is that chronic social and economic stressors result in ancestry-dependent molecular responses that create a tumor permissive tissue microenvironment in normal breast tissue. Altered regulation of N-glycosylation of proteins, a glucose metabolism-linked post-translational modification attached to an asparagine (N) residue, has been associated with two strong independent risk factors for breast cancer: increased breast density and body mass index (BMI). Interestingly, high body mass index (BMI) levels have been reported to associate with increases of cancer-associated N-glycan signatures. In this study, we used matrix assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) to investigate molecular pattern changes of N-glycosylation in ancestry defined normal breast tissue from BW and WW with significant 5-year risk of breast cancer by Gail score. N-glycosylation was tested against social stressors including marital status, single, education, economic status (income), personal reproductive history, the risk factors BMI and age. Normal breast tissue microarrays from the Susan G. Komen tissue bank (BW=43; WW= 43) were used to evaluate glycosylation against socioeconomic stress and risk factors. One specific N-glycan (2158 m/z) appeared dependent on ancestry with high sensitivity and specificity (AUC 0.77, Brown/Wilson p-value<0.0001). Application of a linear regression model with ancestry as group variable and socioeconomic covariates as predictors identified a specific N-glycan signature associated with different socioeconomic stresses. For WW, household income was strongly associated to certain N-glycans, while for BW, marital status (married and single) was strongly associated with the same N-glycan signature. Current work focuses on understanding if combined N-glycan biosignatures can further help understand normal breast tissue at risk. This study lays the foundation for understanding the complexities linking socioeconomic stresses and molecular factors to their role in ancestry dependent breast cancer risk.
format Online
Article
Text
id pubmed-9273232
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92732322022-07-12 Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer Rujchanarong, Denys Scott, Danielle Park, Yeonhee Brown, Sean Mehta, Anand S. Drake, Richard Sandusky, George E. Nakshatri, Harikrishna Angel, Peggi M. Front Oncol Oncology A primary difference between black women (BW) and white women (WW) diagnosed with breast cancer is aggressiveness of the tumor. Black women have higher mortalities with similar incidence of breast cancer compared to other race/ethnicities, and they are diagnosed at a younger age with more advanced tumors with double the rate of lethal, triple negative breast cancers. One hypothesis is that chronic social and economic stressors result in ancestry-dependent molecular responses that create a tumor permissive tissue microenvironment in normal breast tissue. Altered regulation of N-glycosylation of proteins, a glucose metabolism-linked post-translational modification attached to an asparagine (N) residue, has been associated with two strong independent risk factors for breast cancer: increased breast density and body mass index (BMI). Interestingly, high body mass index (BMI) levels have been reported to associate with increases of cancer-associated N-glycan signatures. In this study, we used matrix assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) to investigate molecular pattern changes of N-glycosylation in ancestry defined normal breast tissue from BW and WW with significant 5-year risk of breast cancer by Gail score. N-glycosylation was tested against social stressors including marital status, single, education, economic status (income), personal reproductive history, the risk factors BMI and age. Normal breast tissue microarrays from the Susan G. Komen tissue bank (BW=43; WW= 43) were used to evaluate glycosylation against socioeconomic stress and risk factors. One specific N-glycan (2158 m/z) appeared dependent on ancestry with high sensitivity and specificity (AUC 0.77, Brown/Wilson p-value<0.0001). Application of a linear regression model with ancestry as group variable and socioeconomic covariates as predictors identified a specific N-glycan signature associated with different socioeconomic stresses. For WW, household income was strongly associated to certain N-glycans, while for BW, marital status (married and single) was strongly associated with the same N-glycan signature. Current work focuses on understanding if combined N-glycan biosignatures can further help understand normal breast tissue at risk. This study lays the foundation for understanding the complexities linking socioeconomic stresses and molecular factors to their role in ancestry dependent breast cancer risk. Frontiers Media S.A. 2022-06-27 /pmc/articles/PMC9273232/ /pubmed/35832545 http://dx.doi.org/10.3389/fonc.2022.876651 Text en Copyright © 2022 Rujchanarong, Scott, Park, Brown, Mehta, Drake, Sandusky, Nakshatri and Angel https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Rujchanarong, Denys
Scott, Danielle
Park, Yeonhee
Brown, Sean
Mehta, Anand S.
Drake, Richard
Sandusky, George E.
Nakshatri, Harikrishna
Angel, Peggi M.
Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer
title Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer
title_full Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer
title_fullStr Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer
title_full_unstemmed Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer
title_short Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer
title_sort metabolic links to socioeconomic stresses uniquely affecting ancestry in normal breast tissue at risk for breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273232/
https://www.ncbi.nlm.nih.gov/pubmed/35832545
http://dx.doi.org/10.3389/fonc.2022.876651
work_keys_str_mv AT rujchanarongdenys metaboliclinkstosocioeconomicstressesuniquelyaffectingancestryinnormalbreasttissueatriskforbreastcancer
AT scottdanielle metaboliclinkstosocioeconomicstressesuniquelyaffectingancestryinnormalbreasttissueatriskforbreastcancer
AT parkyeonhee metaboliclinkstosocioeconomicstressesuniquelyaffectingancestryinnormalbreasttissueatriskforbreastcancer
AT brownsean metaboliclinkstosocioeconomicstressesuniquelyaffectingancestryinnormalbreasttissueatriskforbreastcancer
AT mehtaanands metaboliclinkstosocioeconomicstressesuniquelyaffectingancestryinnormalbreasttissueatriskforbreastcancer
AT drakerichard metaboliclinkstosocioeconomicstressesuniquelyaffectingancestryinnormalbreasttissueatriskforbreastcancer
AT sanduskygeorgee metaboliclinkstosocioeconomicstressesuniquelyaffectingancestryinnormalbreasttissueatriskforbreastcancer
AT nakshatriharikrishna metaboliclinkstosocioeconomicstressesuniquelyaffectingancestryinnormalbreasttissueatriskforbreastcancer
AT angelpeggim metaboliclinkstosocioeconomicstressesuniquelyaffectingancestryinnormalbreasttissueatriskforbreastcancer