Associations of childhood, adolescence, and midlife cognitive function with DNA methylation age acceleration in midlife.

Prior studies showed increased age acceleration (AgeAccel) is associated with worse cognitive function among old adults. We examine the associations of childhood, adolescence and midlife cognition with AgeAccel based on DNA methylation (DNAm) in midlife. Data are from 359 participants who had cognition measured in childhood and adolescence in the Child Health and Development study, and had cognition, blood based DNAm measured during midlife in the Disparities study.

Neighborhood Deprivation and Breast Cancer Mortality Among Black and White Women.

Importance: Neighborhood deprivation has been associated with increased breast cancer mortality among White women, but findings are inconsistent among Black women, who experience different neighborhood contexts. Accounting for interactions among neighborhood deprivation, race, and other neighborhood characteristics may enhance understanding of the association.

Objective: To investigate whether neighborhood deprivation is associated with breast cancer mortality among Black and White women and whether interactions with rurality, residential mobility, and racial composition, which are markers of access, social cohesion, and segregation, respectively, modify the association.

Increasing access, equitability, and rigor in the assessment of Neighborhood Mortgage Discrimination.

Mortgage discrimination alters the distribution of investment, opportunity, and economic advantage-key contributors of health disparities. Leveraging Home Mortgage Disclosure Act data, we assessed mortgage denial risk in 380 U.S.

Historical Redlining, Persistent Mortgage Discrimination, and Race in Breast Cancer Outcomes.

Importance: Inequities created by historical and contemporary mortgage discriminatory policies have implications for health disparities. The role of persistent mortgage discrimination (PMD) in breast cancer (BC) outcomes has not been studied.

Objective: To estimate the race-specific association of historical redlining (HRL) with the development of BC subtypes and late-stage disease and a novel measure of PMD in BC mortality.

A Comparison of Three Area-Level Indices of Neighborhood Deprivation and Socioeconomic Status and their Applicability to Breast Cancer Mortality.

Neighborhood deprivation indices are widely used in research, but the performance of these indices has rarely been directly compared in the same analysis. We examined the Area Deprivation Index, Neighborhood Deprivation Index, and Yost index, and compared their associations with breast cancer mortality. Indices were constructed for Georgia census block groups using 2011-2015 American Community Survey data.

Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors.

Importance: The biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood.

Objective: To determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer.

Design, Setting, And Participants: This cross-sectional study collected breast tissue from women undergoing surgery for breast cancer between January 1, 1993, and December 31, 2003.

Census Tracts Are Not Neighborhoods: Addressing Spatial Misalignment in Studies Examining the Impact of Historical Redlining on Present-day Health Outcomes.

Background: Research examining the effects of historical redlining on present-day health outcomes is often complicated by the misalignment of contemporary census boundaries with the neighborhood boundaries drawn by the US Home Owners' Loan Corporation (HOLC) in the 1930s. Previous studies have used different approaches to assign historical HOLC grades to contemporary geographies, but how well they capture redlining exposure is unknown.

Methods: Our analysis included 7711 residences identified in the Multiple Listing Service database in Atlanta, Georgia (2017-2022).

Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome.

Purpose: Place-based measures of structural racism have been associated with breast cancer mortality, which may be driven, in part, by epigenetic perturbations. We examined the association between contemporary redlining, a measure of structural racism at the neighborhood level, and DNA methylation in breast tumor tissue.

Methods: We identified 80 Black and White women diagnosed and treated for a first-primary breast cancer at Emory University Hospitals (2008-2017).

Drivers of racial, regional, and socioeconomic disparities in late-stage breast cancer mortality.

Background: The authors identified tumor, treatment, and patient characteristics that may contribute to differences in breast cancer (BC) mortality by race, rurality, and area-level socioeconomic status (SES) among women diagnosed with stage IIIB-IV BC in Georgia.

Methods: Using the Georgia Cancer Registry, 3084 patients with stage IIIB-IV primary BC (2013-2017) were identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing mortality among non-Hispanic Black (NHB) versus non-Hispanic White (NHW), residents of rural versus urban neighborhoods, and residents of low- versus high-SES neighborhoods by tumor, treatment, and patient characteristics.

Time to Surgical Treatment and Facility Characteristics as Potential Drivers of Racial Disparities in Breast Cancer Mortality.

Background: Black women are more likely to die of breast cancer than White women. This study evaluated the contribution of time to primary surgical management and surgical facility characteristics to racial disparities in breast cancer mortality among both Black and White women.

Methods: The study identified 2224 Black and 3787 White women with a diagnosis with stages I to III breast cancer (2010-2014).

Linking Environmental Exposures to Molecular Pathogenesis in Non-Hodgkin Lymphoma Subtypes.

Non-Hodgkin lymphoma comprises a heterogeneous group of hematologic malignancies, with about 60 subtypes that arise via various pathogenetic mechanisms. Although establishing etiology for specific NHL subtypes has been historically difficult given their relative rarity, environmental exposures have been repeatedly implicated as risk factors across many subtypes. Large-scale epidemiologic investigations have pinpointed chemical exposures in particular, but causality has not been established, and the exact biologic mechanisms underpinning these associations are unclear.

A Signature That May Be Predictive of Early Versus Late Recurrence After Radiation Treatment for Breast Cancer That May Inform the Biology of Early, Aggressive Recurrences.

Purpose: Unmet clinical needs in breast cancer (BC) management include the identification of patients at high risk of local failure despite adjuvant radiation and an understanding of the biology of these recurrences. We previously reported a radiation response signature and here extend those studies to identify a signature predictive of recurrence timing (before or after 3 years).

Methods And Materials: Two independent patient cohorts were used.

Seviteronel, a Novel CYP17 Lyase Inhibitor and Androgen Receptor Antagonist, Radiosensitizes AR-Positive Triple Negative Breast Cancer Cells.

Increased rates of locoregional recurrence (LR) have been observed in triple negative breast cancer (TNBC) despite multimodality therapy, including radiation (RT). Recent data suggest inhibiting the androgen receptor (AR) may be an effective radiosensitizing strategy, and AR is expressed in 15-35% of TNBC tumors. The aim of this study was to determine whether seviteronel (INO-464), a novel CYP17 lyase inhibitor and AR antagonist, is able to radiosensitize AR-positive (AR+) TNBC models.

TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination.

Increased rates of locoregional recurrence are observed in patients with basal-like breast cancer (BC) despite the use of radiation therapy (RT); therefore, approaches that result in radiosensitization of basal-like BC are critically needed. Using patients' tumor gene expression data from 4 independent data sets, we correlated gene expression with recurrence to find genes significantly correlated with early recurrence after RT. The highest-ranked gene, TTK, was most highly expressed in basal-like BC across multiple data sets.

PARP1 Inhibition Radiosensitizes Models of Inflammatory Breast Cancer to Ionizing Radiation.

Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC), with local control rates of 80% or less at 5 years. Given the unsatisfactory outcomes for these patients, there is a clear need for intensification of local therapy, including radiation. Inhibition of the DNA repair protein PARP1 has had little efficacy as a single agent in breast cancer outside of studies restricted to patients with BRCA mutations; however, PARP1 inhibition (PARPi) may lead to the radiosensitization of aggressive tumor types.