Race-stratified Analysis Research Articles

Large-scale analysis highlights obesity as a risk factor for chronic, non-communicable inflammatory diseases

BackgroundOverweight and obesity are a global pandemic, contributing to death and disability-adjusted life-years. Obesity is a major factor in the onset of chronic inflammatory diseases (CIDs). Yet, several knowledge gaps remain: For several CIDs, inconsistent results have been reported, relating to their obesity-imposed risk, data on most rare CIDs remain unavailable, sex differences and racial disparities remain mostly unaddressed.MethodsA large-scale cohort study compared the risk of developing 46 CIDs in individuals with overweight/obesity (n=3,101,824) to an equal number of non-overweight/obese individuals. Propensity score matching optimized between-group comparability, and sensitivity analyses assessed study robustness.ResultsThe risk of developing any CID was 28.48% in overweight/obese individuals versus 17.55% in non-overweight/obese controls, with a hazard ratio (95%-confidence interval) of 1.52 (1.509-1.521, p<0.0001). This risk was consistent across all sensitivity, sex-, and race-stratified analyses. Overweight and obesity were associated with an increased risk for 24 of 46 CIDs in the primary analysis and all sensitivity analyses. For 12 diseases, increased risks were confirmed to one of the two sensitivity analyses, while for 10 diseases, results were discordant. No increased risk was observed for one disease. In sex-stratified analysis, overweight and obesity posed a more pronounced risk for four CIDs in female individuals. In race-stratified analysis, overweight and obesity were linked to a higher risk for seven CIDs in White individuals and to one CID in “Black or African American” individuals.ConclusionOverweight and obesity increase the risk for the majority of CIDs in a sex- and race-specific manner.

Evaluation of the Immune Response within the Tumor Microenvironment in African American and Non-Hispanic White Patients with Non-Small Cell Lung Cancer.

African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in immune response have been minimal. Therefore, we compared components of the tumor microenvironment among African Americans and non-Hispanic Whites diagnosed with non-small cell lung cancer based on PDL1 or tertiary lymphoid structure (TLS) status to identify differences of translational relevance. Using a cohort of 280 patients with non-small cell lung cancer from the Inflammation, Health, Ancestry, and Lung Epidemiology study (non-Hispanic White: n = 155; African American: n = 125), we evaluated PDL1 tumor proportion score (<1% vs. ≥1%) and TLS status (presence/absence), comparing differences within the tumor microenvironment based on immune cell distribution and differential expression of genes. Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than non-Hispanic Whites. In addition, gene expression patterns in African American PDL1-positive samples suggest that these tumors contained greater numbers of γδ T cells and resting dendritic cells, along with fewer CD8+ T cells after adjusting for age, sex, pack-years, stage, and histology. Investigation of differential expression of B cell/plasma cell-related genes between the two patient populations revealed that two immunoglobulin genes (IGKV2-29 and IGLL5) were associated with decreased mortality risk in African Americans. In the first known race-stratified analysis of tumor microenvironment components in lung cancer based on PDL1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified that may have therapeutic implications. Future investigation of racial variation within the tumor microenvironment may help direct the use of immunotherapy.

Investigating the Black Birth Experience: A Race-Stratified Analysis of Preterm Birth Risk and Exposure to Metropolitan Statistical Area-Level Police-Related Deaths, US 2018–2019

Police-related violence may be a source of chronic stress underlying entrenched racial inequities in reproductive health in the USA. Using publicly available data on police-related fatalities, we estimated total and victim race-specific rates of police-related fatalities (deaths per 100,000 population) in 2018–2019 for Metropolitan Statistical Areas (MSA) and counties within MSAs in the USA. Rates were linked to data on live births by maternal MSA and county of residence. We fit adjusted log-Poisson models with generalized estimating equations and cluster-robust standard errors to estimate the relative risk of preterm birth associated with the middle and highest tertiles of police-related fatalities compared to the lowest tertile. We included a test for heterogeneity by maternal race/ethnicity and additionally fit race/ethnicity-stratified models for associations with victim race/ethnicity-specific police-related fatality rates. Fully adjusted models indicated significant adverse associations between police-related fatality rates and relative risk of preterm birth for the total population, non-Hispanic Black, and non-Hispanic White groups separately. Results confirm the role of fatal police violence as a social determinant of population health outcomes and inequities, including preterm birth.

Disease Burden and Health-Related Quality of Life (HRQoL) of Chronic Obstructive Pulmonary Disease (COPD) in the US - Evidence from the Medical Expenditure Panel Survey (MEPS) from 2016-2019.

Chronic obstructive pulmonary disease (COPD) is a progressive disease associated with reduced life expectancy, increased morbidity, mortality, and cost. This study characterized the US COPD burden, including socioeconomic and health-related quality of life (HRQoL) outcomes. In this retrospective, cross-sectional study using nationally representative estimates from Medical Expenditures Survey (MEPS) data (2016-2019), adults (≥18 years) living with and without COPD were identified. Adults living without COPD (control cohort) and with COPD were matched 5:1 on age, sex, geographic region, and entry year. Demographics, clinical characteristics, socioeconomic, and generic HRQoL measures were examined to include a race-stratified analysis of people living with COPD. A total of 4,135 people living with COPD were identified; the matched dataset represented a weighted non-institutionalized population of 11.3 million with and 54.2 million people without COPD. Among people living with COPD, 66.3% had ≥1 COPD-related condition; 62.7% had ≥1 cardiovascular condition, compared to 33.5% and 50.5% without COPD. More people living with COPD were unemployed (56.2% vs 45.3%), unable to work due to illness/disability (30.1% vs 12.1%), had problems paying bills (16.1% vs 8.8%), reported poorer perceived health (fair/poor: 36.2% vs 14.4%), missed more working days due to illness/injury per year (median, 2.5 days vs 0.0 days), and had limitations in physical functioning (40.1% vs 19.4%) (all P<0.0001). In race-stratified analyses for people living with COPD, people self-reporting as Black had higher prevalence of cardiovascular-risk conditions, poorer socioeconomic and HRQoL outcomes, and higher healthcare expenses than White or Other races. Adults living with COPD had higher clinical disease burden, lower socioeconomic status, and reduced HRQoL than those without, with greater disparities among Black people living with COPD compared to White and other races. Understanding the characteristics of patients helps address care disparities and access challenges.

Exploring the incidence of peripheral arterial occlusive disease following COVID-19 infection: A retrospective cohort study.

Peripheral arterial occlusive disease (PAOD) is a clinical manifestation of systemic atherosclerosis and is always associated with cerebrovascular disease and various complications. The aim of our study is to evaluate the relationship between the coronavirus disease 2019 (COVID-19) infection and the subsequent PAOD development. A retrospective cohort study was conducted and individuals with COVID-19 infection were identified from the TriNetX analytics platform. A total of 2 206 065 patients with COVID-19 infection and 2 206 065 patients without COVID-19 infection were recruited after exclusion and matching. The primary outcome was the development of PAOD after the COVID-19 infection. The Cox proportional hazard regression was adopted to yield the hazard ratio (HR) and 95% confidence interval (CI) of PAOD between groups. After the whole follow-up period, the incidence of PAOD was significantly higher in the COVID-19 group at both the 3-month follow-up (HR: 1.27, 95% CI: 1.24-1.30) and the 12-month follow-up (HR: 1.33, 95% CI: 1.31-1.35) The Kaplan-Meier analysis with the log-rank test demonstrated a higher cumulative probability of PAOD in the COVID-19 group compared to the non-COVID-19 group (p < 0.001). In stratified analysis using 65 years as the threshold, both age groups in the COVID-19 group exhibited a higher risk of PAOD. Similarly, in the sex and race stratified analysis, the COVID-19 group performed a higher risk of PAOD in both subgroups. In conclusion, the COVID-19 infections are strongly associated with an increment of PAOD incidence.

547 - Clinical burden and work productivity impairment in moderate-to-severe atopic dermatitis patients in the United States

Abstract Introduction/Background Atopic dermatitis (AD) is a common chronic condition affecting 5-10% of adults worldwide. AD symptoms (e.g., itching) can lead to sleep disturbances and affect daily activity and work productivity. Objectives With the evolving treatment landscape for moderate-to-severe AD, including advanced systemic therapies like biologics and Janus-kinase (JAK) inhibitors, a contemporary appraisal of the clinical burden and impairment in patients with moderate-to-severe AD in the United States (US) is warranted. Methods A web-based survey was conducted in June 2023 among US adults (≥ 18 years) with self-reported moderate-to-­severe AD or who had experience with systemic therapy, were diagnosed with AD for ≥ 1 year, and with inadequate response to topical treatments. Demographic and clinical characteristics (e.g., comorbidities, body regions ever affected by AD) at the time of the survey were summarized descriptively, along with productivity/activity burden (i.e., activity impairment, work impairment, absenteeism, presenteeism) using the Workers Productivity and Impairment Activity Index (WPAI). Analyses were reported overall and separately for White, Black, and Asian participants. Results 300 participants from all US regions completed the survey (White: 234 [78.0%], Black: 37 [12.3%], Asian: 16 [5.3%], Other/Unknown: 13 [4.4%]). Overall, participants’ mean age was 45 years, 70% were female, and 66% were employed. Half had experienced severe symptoms at any time (50%), and 52% had experience with systemic therapy. At the time of the survey, over 90% of participants were receiving treatment for AD, and 20% self-reported current symptoms as mild (moderate: 69%, severe: 11%). Approximately half reported AD affected their face (46%), neck (52%), or feet (54%) at any time. The most frequently reported comorbidities were anxiety (53%), depression (39%), high blood pressure (25%), allergic rhinitis (24%), and asthma (22%). Most participants (85%) reported some activity impairment due to AD with a mean activity impairment score of 37.6%. A majority (82%) of employed participants reported some work impairment due to AD with a mean overall work impairment score of 38.5%, absenteeism of 7.1% and presenteeism of 36.0%. Race-stratified analysis indicated that Black patients were diagnosed at a younger age, with a numerically higher proportion reporting severe disease (70%) and more affected by AD on the face (54%), neck (68%), and feet (62%) at any time compared to White and Asian patients. All race groups reported substantial activity impairment (33.0%-38.6%) and work impairment (27.2%-39.9%). Conclusions Moderate-to-severe AD is associated with a high disease burden with severity of symptoms across the US population, leading to substantial activity and productivity impairments. Given half of the patients in this study had never received systemic therapy, wider use of available treatment options may improve disease and symptom management, thereby reducing activity and work impairment.

Impact of the cytotoxic T-lymphocyte associated antigen-4 rs231775 A/G polymorphism on cancer risk

Impact of the cytotoxic T-lymphocyte associated antigen-4 rs231775 A/G polymorphism on cancer risk

Abstract 18025: Does Co-Morbid Depression Predict Worse In-Hospital Outcomes in Elderly Patients Primarily Hospitalized With Atrial Fibrillation?: A Nationwide Sex and Race Stratified Analysis

Introduction: Depression is an established risk factor for major adverse cardiac and cerebrovascular events (MACCE). However, the association between depression (DP) and all-cause mortality, as well as stroke in atrial fibrillation (AF) patients, remains understudied. We aim to establish a relationship between depression and MACCE in AF patients. Methods: Using the National Inpatient Sample (2019) and relevant international classification of disease (ICD-10) codes, we identified hospitalizations with AF among elderly patients (age &gt;65) and categorized them into groups with and without depression (DP vs nDP). The primary outcome was all-cause inpatient mortality and stroke in AF-related hospitalizations. Results: The overall prevalence of depression (DP) among elderly patients hospitalized for AF was 10.6% (32810/310,005). The DP cohort contained less number of males (30.4% vs 44.38%), Blacks ( 2.91% vs 5.77%), Hispanics (4.11% vs 4.68%) while more females (69.59% vs 55.62%) and Whites ( 88.7% vs 83.82%). Stroke prevalence was not significantly different (0.8% vs 0.8% OR:0.97, CI:0.85-1.1 p=0.701) whereas all-cause mortality prevalence was lower in the DP cohort (0.9% vs 1%, OR: 0.85, CI:0.75-0.97 p=0.015). Surprisingly, the subgroup analysis revealed that depressed males exhibited significantly higher odds of stroke, and this association persisted even after multivariable analysis (aOR 1.184, CI: 1.12-3.02, p= 0.016)[Fig 1]. All-cause mortality was higher in depressed blacks(2.6% vs 1.4%, OR:1.84, CI:1.21-2.79, p=0.004) and lower in depressed females (0.8% vs 1.1%, OR:0.78 CI:0.67-0.91, p=0.001). Adjusted multivariable analysis revealed no significant all-cause mortality and stroke in depressed vs non-depressed except for subgroup analysis for elderly depressed males. Conclusion: Depression independently associated with stroke in elderly males hospitalized for AF.

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

The biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood. To determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer. This cross-sectional study collected breast tissue from women undergoing surgery for breast cancer between January 1, 1993, and December 31, 2003. Participants were recruited through the University of Maryland Medical Center, with additional collection sites at Baltimore-area hospitals. Data analysis was performed from March 1 through December 1, 2022. Year 2000 census tract-level socioeconomic deprivation measured via neighborhood deprivation index (NDI) as a standardized score, with Black and White race being ascertained through self-report. The primary outcome was tissue DNA methylation using genome-wide measurements. The secondary outcome was tissue gene expression. Participants included 185 women with breast cancer (110 Black [59.5%], 75 White [40.5%]). Mean (SD) age at surgery was 56.0 (14.1) years. Neighborhood deprivation was higher for Black women than for White women (Mean [SD] NDI, 2.96 [3.03] for Black women and -0.54 [1.91] for White women; difference, -3.50; 95% CI, -4.22 to -2.79; P < .001). In unstratified analysis, 8 hypomethylated CpG sites were identified as associated with the NDI, including sites in 2 tumor suppressor genes, LRIG1 and WWOX. Moreover, expression of the 2 genes inversely correlated with neighborhood deprivation. In the race-stratified analysis, the negative correlation between the LRIG1 gene body CpG site cg26131019 and the NDI remained significant in Black women. A neighborhood deprivation-associated decrease in gene expression was also observed for LRIG1 and WWOX in tumors from Black women. In this study, high neighborhood deprivation was associated with differences in tissue DNA methylation and gene expression among Black women. These findings suggest that continued investment in public health interventions and policy changes at the neighborhood level may help to remedy biological alterations that could make minoritized populations more susceptible to chronic diseases.

Psychosocial and structural stressors and engagement in medical care among young sexual minority men across racial identities

Psychosocial and structural stressors and low engagement in medical care likely contribute to the disproportionate burden of chronic disease among sexual minority men (SMM) across the life course. However, how these stressors impact engagement in medical care among young SMM (YSMM) across racial identities remains understudied. The association of psychosocial and structural stressors with forgoing care among YSMM across racial identities was examined using race-stratified adjusted logistic regression of cross-sectional data. Among 737 HIV-negative SMM aged 16–24 years, nearly all (93%) experienced discrimination in their daily lives. Non-Hispanic/Latinx Black participants reported significantly higher levels of discrimination, exposure to community violence, and food insecurity. Medical mistrust and mental health were not significantly different across racial groups. In the full sample model, education, food insecurity, and discrimination were associated with forgoing care. Among the non-Hispanic/Latinx White sample, medical mistrust and discrimination were associated with forgoing care. Among the non-Hispanic/Latinx Black sample, discrimination was associated with forgoing care. Among the Hispanic/Latinx sample, food insecurity was associated with forgoing care. Psychosocial and structural stressors were common in this YSMM cohort, and significantly different across racial/ethnic identities. Race-stratified analysis revealed differences in the association of stressors with forgoing care among YSMM across racial identities, not appreciated in the analysis limited to the total study population. Our findings may support efforts to address health inequity and improve engagement in medical care among SMM.

44255 Impact of acne on social functioning, emotional functioning, and activities of daily living(ADL) among patients with moderate to severe non-nodular Acne Vulgaris (AV) administered sarecycline in community practices across the U.S: Race stratified analysis

44255 Impact of acne on social functioning, emotional functioning, and activities of daily living(ADL) among patients with moderate to severe non-nodular Acne Vulgaris (AV) administered sarecycline in community practices across the U.S: Race stratified analysis

44248 Patient Reported Outcomes (PROs) assessed using Acne Symptom and Impact Scale (ASIS) among patients with moderate to severe non-nodular Acne Vulgaris (AV) administered sarecycline in community practices across the U.S: Race stratified analysis of PROSES

44248 Patient Reported Outcomes (PROs) assessed using Acne Symptom and Impact Scale (ASIS) among patients with moderate to severe non-nodular Acne Vulgaris (AV) administered sarecycline in community practices across the U.S: Race stratified analysis of PROSES

The correlation between the serum LDL-C/Apo B ratio and lumbar bone mineral density in young adults

BackgroundNumerous studies have confirmed that atherosclerosis is related to osteoporosis (OP), and patients with atherosclerosis are more prone to OP. The ratio of low-density lipoprotein cholesterol (LDL-C) to apolipoprotein B (Apo B) is the valid indicator of atherosclerosis. Nevertheless, conclusions regarding relation between LDL-C/Apo B ratio and bone mineral density (BMD) are still lacking. As a result, this study concentrated on investigating the relationship between LDL-C/Apo B ratio and lumbar BMD in the young adult population according to the National Health and Nutrition Examination Survey (NHANES).MethodsInformation of 2027 young adults (age 20–40 years) from NHANES database was obtained for this cross-sectional study. The correlation between serum LDL-C/Apo B ratio and lumbar BMD was explored through weighted multiple stratified linear regression, while the smooth curve fitting model was utilized for analyzing nonlinear relation. In the nonlinear relation, the inflection point was calculated by saturation threshold analysis. The weighted two-piecewise linear regression model was constructed.ResultsAfter covariates were adjusted, the relation between serum LDL-C/Apo B ratio and lumbar BMD varied by sex (males: β = -0.0126, 95% CI -0.0892, 0.0640; females: β = 0.0322, 95% CI -0.0367, 0.1011). By performing age-stratified subgroup analysis, the association also varied by age and sex. Males aged 20–30 years presented a negative trend (β = -0.0570, 95% CI -0.1656, 0.0517), and males with the age of 31–40 years showed a positive trend (β = 0.0810, 95% CI -0.0312, 0.1931). Women showed a positive trend by age (females of 20–30 years: β = 0.0051, 95% CI -0.0935, 0.1036; females of 31–40 years: β = 0.0265, 95% CI -0.0767, 0.1296). In race-stratified subgroup analysis, the relations varied by sex and race. To be specific, non-Hispanic black males showed a negative trend (β = -0.0754, 95% CI -0.2695, 0.1188), and males of other races exhibited a positive trend. The trend was positive for women of all races.ConclusionDifferences were detected in the association between serum LDL-C/Apo B ratio and lumbar BMD among cases aged 20–40 years across sex, age, and race/ethnicity. In addition, the inflection points in U-shaped relationships were also calculated.

Rising trend of acute myocardial infarction among young cannabis users: A 10-year nationwide gender and race stratified analysis

The use of cannabis has massively increased among younger patients due to increasing legalization and availability. We performed a retrospective nationwide study using the Nationwide inpatient sample (NIS) database to analyze the trends of acute myocardial infarction (AMI) in young cannabis users and related outcomes among patients aged 18-49 years from 2007 to 2018, using ICD-9 and ICD-10 codes. Out of 819,175 hospitalizations, 230,497 (28%) admissions reported using cannabis. There was a significantly higher number of males (78.08% vs. 71.58%, p<0.0001) and African Americans (32.22% vs. 14.06%, p<0.0001) admitted with AMI and reported cannabis use. The incidence of AMI among cannabis users consistently increased from 2.36% in 2007 to 6.55% in 2018. Similarly, the risk of AMI in cannabis users among all races increased, with the biggest increase in African Americans from 5.69% to 12.25%. In addition, the rate of AMI in cannabis users among both sexes showed an upward trend, from 2.63% to 7.17% in males and 1.62%-5.12% in females. The incidence of AMI in young cannabis users has increased in recent years. The risk is higher among males and African Americans.

Proteomics Analysis of Genetic Liability of Abdominal Aortic Aneurysm Identifies Plasma Neogenin and Kit Ligand: The ARIC Study.

Genome-wide association studies have reported 23 gene loci related to abdominal aortic aneurysm (AAA)-a potentially lethal condition characterized by a weakened dilated vessel wall. This study aimed to identify proteomic signatures and pathways related to these risk loci to better characterize AAA genetic susceptibility. Plasma concentrations of 4870 proteins were determined using a DNA aptamer-based array. Linear regression analysis estimated the associations between the 23 risk alleles and plasma protein levels with adjustments for potential confounders in a race-stratified analysis of 1671 Black and 7241 White participants. Significant proteins were then evaluated for their prediction of clinical AAA (454 AAA events in 11 064 individuals), and those significantly associated with AAA were further interrogated using Mendelian randomization analysis. Risk variants proximal to PSRC1-CELSR2-SORT1, PCIF1-ZNF335-MMP9, RP11-136O12.2/TRIB1, ZNF259/APOA5, IL6R, PCSK9, LPA, and APOE were associated with 118 plasma proteins in Whites and 59 were replicated in Black participants. Novel associations with clinical AAA incidence were observed for kit ligand (HR, 0.59 [95% CI, 0.42-0.82] for top versus first quintiles) and neogenin (HR, 0.64 [95% CI, 0.46-0.88]) over a median 21.2-year follow-up; neogenin was also associated with ultrasound-detected asymptomatic AAA (N=4295; 57 asymptomatic AAA cases). Mendelian randomization inverse variance weighted estimates suggested that AAA risk is promoted by lower levels of kit ligand (OR per SD=0.67; P=1.4×10-5) and neogenin (OR per SD=0.50; P=0.03). Low levels of neogenin and kit ligand may be novel risk factors for AAA development in potentially causal pathways. These findings provide insights and potential targets to reduce AAA susceptibility.

Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease.

Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Abstract 1961: Discovery and validation of prostate cancer biomarkers of biochemical recurrence in low-risk prostate cancer patients

Abstract Introduction: Prostate cancer (CaP) is predominantly indolent disease with a small fraction of patients undergoing metastatic progression. Therefore, it is critical to identify prognostic markers for the early detection of an aggressive subtype. We hypothesized that tissue specimens from early-stage, low risk CaP may harbor predictive prognostic signatures for disease progression after radical prostatectomy. Previously, we had systematically evaluated and optimized the NanoString platform for CaP gene expression analysis in formalin fixed paraffin embedded (FFPE) whole mounted prostate specimens. The goal of the study is to validate the CPDR findings on the differential mRNA expression of candidate markers from patients with BCR (biochemical recurrence) and non-BCR in an independent cohort. Methods: This is a retrospective case cohort study based on 78 tumor-normal paired (N=156) archived whole mounted FFPE prostate samples received from biobank at UTHSCSA. We performed an optimized NanoString analysis of 203-CaP probe set to evaluate the association of markers with BCR outcome in a racially diverse patient population comprising of 21.6% AA and 78.38% CA men. The cohort comprised of 28 patients with BCR, and 50 patients with no BCR (based on a minimum of 5 years of follow-up). ERG gene expression was validated by immunohistochemistry (IHC) assay using CPDR ERG-MAb (9FY). Normalized nCounter gene expression data was analyzed using the NanoString nSolver (v 4.0) platform. Fisher exact and Wilcoxon-Mann-Whitney tests were used for categorical and continuous variables respectively. Results: We found 96.1% (73/76) concordance between ERG IHC and NanoString datasets, which provides strong QC and validation for NanoString data. ERG positive tumors had strong expression of both TMPRSS2-ERG fusion and several other ERG splice forms. Additionally, the prostate epithelial cell markers PSA, MSMB and PAP had the highest signals in all samples reflecting the prostate epithelial origin of the specimens. Differential gene expression analysis showed that a total of 37 genes were found to be significantly (P adj &amp;lt;0.05) different across tumors and normal. Established CaP genes like AMACR, PCA3, OR51E2, ERG, HOXC6, DLX1, CACNA1D and PSGR were most highly over-expressed in tumors compared to matched normal while GSTP1, CAV1, PAP and MSMB were significantly downregulated in tumors compared to adjacent normal prostate epithelia. Race stratified analysis in this randomly selected patient cohort showed that AA men were found to be significantly younger (median age: 56 years AA vs. 63 years CA; p 0.01) and had higher frequency of BCR events (p 0.004) than CA men. Data analysis for disease outcome across AA and CA men is ongoing. Conclusions: We confirmed that NanoString approach is useful for evaluation of prognostic biomarker candidates in prostate cancer using FFPE specimens. Citation Format: Indu Kohaar, Kaitlyn Bejar, Denise Young, Yingjie Song, Jiji Jiang, Jacob Kagan, Sudhir Srivastava, Javier Hernandez, Gregory Chesnut, Isabell A. Sesterhenn, Robin J. Leach, Gyorgy Petrovics. Discovery and validation of prostate cancer biomarkers of biochemical recurrence in low-risk prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1961.

Abstract 3676: Race-specific methylation profiles and epigenetic age acceleration differentiates estrogen receptor status breast cancer

Abstract Breast cancer (BrCa) is the second most common cancer among women in the U.S.. Black women with BrCa, on average, have an earlier age of onset, more aggressive subtypes and experience higher mortality compared with White women. Although the underlying causes remain unknown, genetic and lifetime exposures are hypothesized. Here, we utilize blood-based whole-genome methylation arrays to: (1) discover CpG probes related to BrCa receptor status, (2) identify biological pathways driving BrCa subtype disparities, and (3) quantify epigenetic age acceleration differences by race and receptor status. DNA methylation levels were generated for 95 blood samples from women diagnosed with BrCa using the Illumina EPIC array. After quality control, M-values for 91 samples and 808,329 methylation probes were evaluated using a modified Student t-test. BrCa estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status were collected from health records. Stratified analyses by race adjusting for age were applied. We calculated the association of age acceleration, based on Horvath’s epigenetic clock, by race and receptor status. Statistical significance, corrected for multiple testing, was defined as a p-valueadj &amp;lt;0.05. Among the 91 BrCa samples, nearly half were Black women (40.7%) and the overall mean age at diagnosis was 56.5 years ±11.3. The majority of BrCa tumors were ER-, 60.4% (N=55), and HER2-, 76.9% (N=70). Overall, two methylation probes significantly differentiated ER+/- BrCa. The most significant methylated gene was FOXK2 (p-valueadj=0.03, logFC=0.63). The race-stratified analysis identified 188,398 probes for ER+/- and five probes for HER2+/- among White women as marginally significant (p&amp;lt;0.05). Two genes (FAM107B, PRKCZ) for ER+/- BrCa and four genes (ZNF430, TTC27, SEC1 and NOS1AP) for HER2+/- BrCa remained statistically significant after correcting for multiple comparisons (p-valueadj &amp;lt; 0.05; |logFC| &amp;gt;1). The mean age acceleration is estimated as 3.7 years greater for Black women compared to White women. Among White women, the mean age acceleration was 1.9 years greater for ER+ than ER- subtypes, and those HER2- were 2.2 years older than HER2+. Similarly, among Black women the mean age acceleration difference for ER- was 3.2 years greater than ER+, and HER2- was 3.8 years older than HER2+. Our study confirmed (e.g. FOXK2) and identified several novel methylation sites associated with BrCa subtypes. Furthermore, we demonstrated in our study that epigenetic age acceleration of BrCa varies by race, with Black women biologically aging faster than White women. Although this is a limited sample size, stratified analyses revealed biological age differences by race and receptor status. In-depth pathway analyses and measuring additional samples are underway. Lastly, differential methylation profiles for known risk factors of aggressive tumors will be evaluated. Citation Format: Yanning Wu, Cheryl L. Thompson, Fredrick R. Schumacher. Race-specific methylation profiles and epigenetic age acceleration differentiates estrogen receptor status breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3676.

Structural Racism and Breast Cancer-specific Survival: Impact of Economic and Racial Residential Segregation.

To analyze the effect of economic and racial/ethnic residential segregation on breast cancer-specific survival (BCSS) in South Florida, a diverse metropolitan area that mirrors the projected demographics of many United States regions. Despite advances in diagnosis and treatment, racial and economic disparities in BCSS. This study evaluates these disparities through the lens of racial and economic residential segregation, which approximate the impact of structural racism. Retrospective cohort study of stage I to IV breast cancer patients treated at our institution from 2005 to 2017. Our exposures include index of concentration at the extremes, a measurement of economic and racial neighborhood segregation, which was computed at the census-tract level using American Community Survey data. The primary outcome was BCSS. Random effects frailty models predicted that patients living in low-income neighborhoods had higher mortality compared to those living in high-income neighborhoods [hazard ratios (HR): 1.56, 95% confidence interval (CI): 1.23-2.00]. Patients living in low-income non-Hispanic Black and Hispanic neighborhoods had higher mortality compared to those living in high-income non-Hispanic White (NHW) neighborhoods (HR: 2.43, 95%CI: 1.72, 3.43) and (HR: 1.99, 95%CI: 1.39, 2.84), after controlling for patient characteristics, respectively. In adjusted race-stratified analysis, NHWs living in low-income non-Hispanic Black neighborhoods had higher mortality compared to NHWs living in high-income NHW neighborhoods (HR: 4.09, 95%CI: 2.34-7.06). Extreme racial/ethnic and economic segregation were associated with lower BCSS. We add novel insight regarding NHW and Hispanics to a growing body of literature that demonstrate how the ecological effects of structural racism-expressed through poverty and residential segregation-shape cancer survival.

Fetal sex and risk of preeclampsia: Dose maternal race matter?

Objective To examine whether maternal race could affect the relationship between fetal sex and preeclampsia. Material and methods This study was a cohort analysis using prospectively collected data from pregnant women who participated in the Vitamin Antenatal Asthma Reduction Trial (VDAART). Preeclampsia was the secondary outcome of VDAART. We examined the association of fetal sex with preeclampsia and its potential interaction with maternal race in 813 pregnant women (8% with preeclampsia) in logistic regression models with adjustment for preterm birth (<37 weeks of gestation), maternal age, education, and body mass index at enrollment and clinical center. We further conducted a race stratified analysis and also examined whether any observed association was dependent on the gestational age at delivery and prematurity. Results In an analysis of all races combined, preeclampsia was not more common among pregnant women with a male fetus compared to those with a female fetus (odds ratio [OR] = 1.3, 95% CI = 0.81, 2.24). There was an interaction between African American race and fetal sex in association with preeclampsia after adjustment for preterm delivery and other potential confounders (p = .014). In race stratified analyses, we observed higher odds of preeclampsia among African American pregnant women who carried male fetuses after adjustment for preterm delivery and other potential confounders (adjusted OR = 2.4, 95% CI = 1.12, 5.60). Conclusion We observed fetal sexual dimorphic differences in the occurrence of preeclampsia in African American women, but not in Whites. Information on fetal sex may ultimately improve the prediction of pre-eclampsia in African American mothers, who might be at higher risk for this adverse condition in pregnancy.