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

Abstract

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.

N-glycan profiling of tissue samples to aid breast cancer subtyping

“…However, these differences were small compared to the expected biological variation in different individuals, with the standard deviation varying between 2 and 5%. Another aspect related to biological variation is the hypothesis that chronic social and economic stressors may be associated with an increased risk of cancer-associated N-glycan signatures in the tissue microenvironment in normal breast tissue 64 .…”

Advances and Emerging Medical Applications of Direct Mass Spectrometry Technologies for Tissue Analysis

“…Another intriguing prognostic application of MALDI MSI is the spatiochemical interrogation of ancestry-specific disparities in cancer incidence and mortality (19,20). Rujchanarong et al (20) recently implemented MALDI MSI to define N-glycosylation patterns in normal breast tissue microarrays, correlating the observed glycan profiles to a variety of socioeconomic factors underlying differential breast cancer risk in Black (n = 43) and White (n = 43) women.…”

“…Another intriguing prognostic application of MALDI MSI is the spatiochemical interrogation of ancestry-specific disparities in cancer incidence and mortality (19,20). Rujchanarong et al (20) recently implemented MALDI MSI to define N-glycosylation patterns in normal breast tissue microarrays, correlating the observed glycan profiles to a variety of socioeconomic factors underlying differential breast cancer risk in Black (n = 43) and White (n = 43) women. For example, the glycan peak at m/z 2,012, identified as Hex5dHex1HexNAc5, was present at higher intensities in breast tissue of White women relative to Black women but was significantly less abundant in obese patients compared to those with a normal body mass index regardless of ancestry.…”

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“…Another intriguing prognostic application of MALDI MSI is the spatiochemical interrogation of ancestry-specific disparities in cancer incidence and mortality (19,20). Rujchanarong et al (20) recently implemented MALDI MSI to define N-glycosylation patterns in normal breast tissue microarrays, correlating the observed glycan profiles to a variety of socioeconomic factors underlying differential breast cancer risk in Black (n = 43) and White (n = 43) women.…”

“…Another intriguing prognostic application of MALDI MSI is the spatiochemical interrogation of ancestry-specific disparities in cancer incidence and mortality (19,20). Rujchanarong et al (20) recently implemented MALDI MSI to define N-glycosylation patterns in normal breast tissue microarrays, correlating the observed glycan profiles to a variety of socioeconomic factors underlying differential breast cancer risk in Black (n = 43) and White (n = 43) women. For example, the glycan peak at m/z 2,012, identified as Hex5dHex1HexNAc5, was present at higher intensities in breast tissue of White women relative to Black women but was significantly less abundant in obese patients compared to those with a normal body mass index regardless of ancestry.…”