African American Population Research Articles

Differences in Clinical Outcomes between Non-Obese African American and Asian Populations Who have Hyperlipidemia

Differences in Clinical Outcomes between Non-Obese African American and Asian Populations Who have Hyperlipidemia

Vitamin D receptor polymorphisms and associated miRNAs in the development of breast cancer in African American women

Breast cancer (BCa) is a prevalent form of cancer in women, exhibiting varying rates and distribution across different ethnic groups. Among these groups, African American (AA) women have the highest incidence of BCa and the lowest levels of Vitamin D (VD). Numerous studies have explored the connection between variations in the VDR gene and BCa risk, particularly in different populations, but research on the AA population remains limited. Epigenetic modifications, including specific microRNAs (miRNAs), can influence gene expression without altering the genetic code and have been implicated in cancer initiation and progression. Our hypothesis suggests that VDR gene variations may increase BCa risk in AA women and that changes in miRNA expression profiles could contribute to BCa development. Using data from the 1000 Genome Project, we identified five VDR gene variants with significant frequency differences between AA and European-American (EA) populations. We genotyped 404 African American BCa cases and controls for five variants using TaqMan® assays. SNPstats assessed their association with BCa risk. The rs1544410 variant’s recessive model (A/A) showed a decreased BCa risk in AA (odds ratio 0.33, 95% CI: 0.15–0.73, p-value 0.0041). Conversely, the rs2853563 variant’s recessive model (A/A) was linked to an increased BCa risk (odds ratio 4.04, 95% CI: 1.49–10.95, p-value 0.0022). We investigated miRNA expression influenced by VD in HCC1806 Triple-Negative Breast Cancer (TNBC) cell lines with the A/A allele for rs2853563. nCounter® Nanostring technology assessed miRNA profiles after calcitriol treatment. Our results indicated that calcitriol treatment led to reduced expression of six miRNAs, four of which are associated with tumor suppression in the presence of the AA genotype in TNBC cell lines. These findings suggest that specific VDR genotypes could have a potential effect on the miRNAs expression which could potentially serve as markers for cell proliferation in TNBC.

Lower Prevalence of Asymptomatic Alzheimer's Disease Among Healthy African Americans.

Alzheimer's disease (AD) is believed to be more common in African Americans (AA), but biomarker studies in AA populations are limited. This report represents the largest study to date examining cerebrospinal fluid AD biomarkers in AA individuals. We analyzed 3,006 cerebrospinal fluid samples from controls, AD cases, and non-AD cases, including 495 (16.5%) self-identified black/AA and 2,456 (81.7%) white/European individuals using cutoffs derived from the Alzheimer's Disease Neuroimaging Initiative, and using a data-driven multivariate Gaussian mixture of regressions. Distinct effects of race were found in different groups. Total Tauand phospho181-Tau were lower among AA individuals in all groups (p < 0.0001), and Aβ42 was markedly lower in AA controls compared with white controls (p < 0.0001). Gaussian mixture of regressions modeling of cerebrospinal fluid distributions incorporating adjustments for covariates revealed coefficient estimates for AA race comparable with 2-decade change in age. Using Alzheimer's Disease Neuroimaging Initiative cutoffs, fewer AA controls were classified as biomarker-positive asymptomatic AD (8.0% vs 13.4%). After adjusting for covariates, our Gaussian mixture of regressions model reduced this difference, but continued to predict lower prevalence of asymptomatic AD among AA controls (9.3% vs 13.5%). Although the risk of dementia is higher, data-driven modeling indicates lower frequency of asymptomatic AD in AA controls, suggesting that dementia among AA populations may not be driven by higher rates of AD. ANN NEUROL 2024;96:463-475.

BIOM-08. CDKN2A --AN INDEPENDENT CYCLIN-DEPENDENT KINASE INHIBITOR VARIANT ASSOCIATED WITH MALIGNANCY AND WITH SMALL VESSEL STROKE, AS A POTENTIAL MARKER FOR RISK OF LARGE-VESSEL STROKE COMPLICATING BENIGN TERATOMA

Abstract BACKGROUND Cyclin-dependent kinase inhibitor variants, particularly those of CDKN2A are known to be associated with autosomal dominant Familial Atypical Multiple Mole/Melanoma Syndrome and pancreatic cancer predisposition. These variants are associated with risk of small vessel stroke in African/ African-American populations, and are risk factors for stroke in Nordic populations with hypertension, independent of cardiovascular risk factors. METHODS We performed a case review of a female presenting in late infancy with a central nervous system teratoma, that later was complicated by a right hemispheric middle cerebral artery (MCA)stroke, associated with a CDKN2A germline mutation. RESULTS This 14month old female presented with transient alterations of consciousness and apparent abdominal migraine events with pernicious vomiting. Neuroimaging revealed a right heterogeneous para- suprasellar mass and bilateral complex arachnoid adjacent cysts. She was observed closely for any progression, as the lesion was immediately adjacent to the optic chiasm. One year after presentation, she developed an acute ischemic right middle cerebral artery (MCA) stroke and had radiographic evidence of severe stenosis and decreased flow primarily within the right supra-clinoid internal carotid artery, the M1 segment and portion of the right A1 segment of cerebral vessels, with decreased enhancement and number of vessels in the distal right MCA territory. The vessels did not appear to be compressed by any mass effect. The radiologic appearance was consistent with vasospasm. The patient upon stoke recovery, underwent near- complete resection of the mass with no evidence of disruption of the capsule surrounding it and no vascular infiltration. Pathology revealed the expected teratoma with prominence of pancreatic acinar structures, and molecular evidence of a variant of CDKN2A, which was present in the patient and mother in the germline. CONCLUSION We propose that the imaging evidence of a vasculopathy was related to the genotype at the cyclin- dependent kinase site.

A Narrative Review of Alzheimer Dementia in African American and Hispanic Populations: The Health Care Provider's Role

African Americans and Hispanics, especially those of advanced age living with chronic diseases, have a higher risk of developing Alzheimer dementia (AD). Poor control of chronic diseases, such as diabetes, lack of awareness of increased risk factors by health care providers, or fragmented provider care can lead to missed opportunities to adopt early assessment strategies that can mitigate the effects or onset of AD. Nurse practitioners and other health care providers can play a crucial role in implementing chronic disease management strategies and educating patients who are at risk for AD among African Americans and Hispanics.

Addressing the Gap: Racial Disparities and Public Health Strategies in the Epidemiology of Gastrointestinal Stromal Tumors.

Background Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal neoplasms of the gastrointestinal tract, arising from the interstitial cells of Cajal. These tumors bridge the nervous system and muscular layers of the gastrointestinal tract, playing a crucial role in the digestive process. The incidence of GISTs demonstrates notable variations across different racial and ethnic groups, underscoring the need for in-depth analysis to understand the interplay of genetic, environmental, and socioeconomic factors behind these disparities. Linear regression analysis is a pivotal statistical tool in such epidemiological studies, offering insights into the temporal dynamics of disease incidence and the impact of public health interventions. Methodology This investigation employed a detailed dataset from 2009 to 2020, documenting GIST incidences across Asian, African American, Hispanic, and White populations. A meticulous preprocessing routine prepared the dataset for analysis, which involved data cleaning, normalization of racial terminologies, and aggregation by year and race. Linear regression models and Pearson correlation coefficients were applied to analyze trends and correlations in GIST incidences across the different racial groups, emphasizing an understanding of temporal patterns and racial disparities in disease incidence. Results The study analyzed GIST cases among four racial groups, revealing a male predominance (53.19%) and an even distribution of cases across racial categories: Whites (27.66%), Hispanics (25.53%), African Americans (24.47%), and Asians (22.34%). Hypertension was the most common comorbidity (32.98%), followed by heart failure (28.72%). The linear regression analysis for Asians showed a decreasing trend in GIST incidences with a slope of -0.576, an R-squared value of 0.717, and a non-significant p-value of 0.153. A significant increasing trend was observed for Whites, with a slope of 0.581, an R-squared value of 0.971, and a p-value of 0.002. African Americans exhibited a moderate positive slope of 0.277 with an R-squared value of 0.470 and a p-value of 0.201, indicating a non-significant increase. Hispanics showed negligible change over time with a slope of -0.095, an R-squared value of 0.009, and a p-value of 0.879, suggesting no significant trend. Conclusions This study examines GIST incidences across racial groups, revealing significant disparities. Whites show an increasing trend (p = 0.002), while Asians display a decreasing trend (p = 0.153), with stable rates in African Americans and Hispanics. Such disparities suggest a complex interplay of genetics, environment, and socioeconomic factors, highlighting the need for targeted research and interventions that address these differences and the systemic inequalities influencing GIST outcomes.

Multiple myeloma in the African American population: A 2010-2020 NCDB analysis.

e19531 Background: Multiple myeloma (MM) exhibits a disproportionately higher prevalence among African American individuals. Various factors contribute to the disease's progression, severity, and prognosis. This analysis presents real-world data from the National Cancer Database (NCDB) from 2010 to 2020. Methods: Cohort of 241,446 MM patients between 2010 and 2020 were analyzed. Demographic variations, including age, gender, insurance status, educational attainment, and median household income, were examined. Multivariate Cox regression analysis was conducted to identify factors influencing survival outcomes. Results: Within the database, from 2010 to 2020, 51,668 cases of multiple myeloma were recorded among Black individuals. The age group most affected was 40 to 65 years (50.2%), followed by those over 65 (47.3%), with 2.5% falling between 18 to 40 years, and a mean age of 64.4 years. Most cases affected females (51.5%), with most households earning less than $40,227 annually. A significant portion of Black patients did not receive a transplant (83.8%) or immune based option (73.1%). The mean duration from diagnosis to therapy initiation was 37.5 days. Multivariate analysis revealed that patients over 65 had a worse prognosis (HR = 1.52, 95% CI: 1.47 – 1.57, P &lt; 0.001) compared to those under 65, while females exhibited a better prognosis (HR = 0.88, 95% CI: 0.86 – 0.91, P &lt; 0.001). Patients with private insurance had better outcomes (HR = 0.73, 95% CI: 0.68 – 0.78, P &lt; 0.001), as did those treated in academic centers (HR = 0.89, 95% CI: 0.87 – 0.92, P &lt; 0.001). Additionally, patients receiving any form of transplant had better outcomes (HR = 0.45, 95% CI: 0.42 - 0.49, P &lt; 0.001), along with those undergoing chemotherapy (HR = 0.73, 95% CI: 0.68 – 0.78, P &lt; 0.001) and immunotherapy (HR = 0.67, 95% CI: 0.64 – 0.69, P &lt; 0.001). Conclusions: The analysis highlights significant demographic and treatment influences among African American patients with MM. Some identifiable factors associated with improved outcomes include younger age, female gender, private insurance, treatment in academic centers, and most importantly receipt of transplant and Immunotherapy. These findings underscore the importance of targeted interventions considering various factors and improving outcomes in this population. [Table: see text]

The effect of resting dendritic cells on overall survival in the hepatocellular carcinoma tumor microenvironment.

e14559 Background: Hepatocellular carcinoma (HCC) continues to have a poor prognosis even in the advent of new immunotherapy regimens. An area of growing interest in HCC is its tumor immune microenvironment. Classifying the immune microenvironment based on available genomics can lead to insights on prognosis and treatment, especially regarding the role of immunotherapy. Methods: RNA sequencing data was extracted from The Cancer Genome Atlas (TCGA), specifically from the hepatocellular carcinoma section (n = 366). CIBERSORT was utilized to organize the immune cell fractions present for each patient sample. Radiant by Shiny was used to perform a linear regression elucidating the relationship between overall survival and several other variables including: age, gender, tumor stage, race, ethnicity, B-cells naïve, B-cells memory, plasma cells, CD8 T-cells, CD4 T-cells, T-cells follicular, T-cells regulatory, natural killer activated and resting cells, monocytes, macrophages (M0, M1, M2), dendritic cells activated and resting, mast cells activated and resting, eosinophils, and neutrophils. Subgroup analyses were also performed via radiant regarding gender, race, and resting dendritic counts. Results: Resting dendritic cells were independently prognostic of overall survival on multivariable analysis (p = 0.041). The coefficient of correlation was +164.53 showing a positive association between the number of resting dendritic cells and the overall survival. Subgroup analysis showed no difference in resting dendritic counts between males and females (p = 0.526). Also, there was no difference seen in resting dendritic counts between populations of Asians and African Americans (p = 0.873), Asians and Whites (p = 0.223), and between Whites and African Americans (p = 0.811). Conclusions: Patients with a higher number of resting dendritic cells in their tumor immune microenvironment had a better overall survival. There was no difference between males and females in the resting dendritic counts. Likewise, there was no difference in the resting dendritic counts between Asian, African American, and white populations. Resting dendritic cells have been shown to be enriched in hepatocellular carcinomas with a low tumor mutational burden. This is a paradigm that should be explored further in the context of immunotherapy. Resting dendritic cells are also in a state of plasticity as they go from resting to active. Future genomic analysis of the tumor microenvironment regarding this plasticity could also lead to enhancing treatment options.

Ethnic disparities in breast cancer: A comprehensive analysis of socio-demographic and clinical characteristics among African American, Hispanic, and Caucasian women.

e13698 Background: Despite advancements in breast cancer therapy leading to a decline in mortality rates within certain ethnic populations, there exists a concerning trend of increasing cancer incidence among African American (AA) and Hispanic women. This persistent rise highlights the urgent need to explore and comprehend the socio-demographic and breast cancer characteristics specific to these populations. Methods: We assembled a 10-year database of women diagnosed with breast cancer in the community hospital in Chicago. After excluding minority ethnic groups, specifically AA, Hispanic, and Caucasian cohorts were included in this study, comprising 786 patient records analyzed. Results: The distribution revealed a predominance of AA patients at 49.7%, Hispanics at 42.1%, and Caucasians at 8.14%. Noteworthy differences across the three ethnic groups were observed in age categories at cancer diagnosis, BMI categories, family history of first-degree relatives with breast cancer, marital status, smoking habits, menopausal status, and alcohol use at the time of diagnosis (p &lt; 0.05). Within the molecular subtypes, 14.5% were identified as triple-negative breast cancer (TNBC), with a higher prevalence of 18.7% among the AA subgroups. 19.6% of patients had advanced disease, proportion was higher in AA ethnic group (22.8%; p = 0.83) compared to other ethnicities. Breast conservative procedures were prevalent in almost half of the patient population on average (52.1 %), with a slightly higher frequency of mastectomies noted in the Hispanic patient group (44.1%, p &lt; 0.05). In logistic regression analysis, compared to the reference AA ethnicity, Hispanics exhibited higher odds of having HER-2 positive breast cancer (OR 1.74; CI 1.04 – 2.94; p &lt; 0.05), as did Caucasians (OR 2.35; CI 1.05 – 5.04; p &lt; 0.05). Conclusions: In summary, our study underscores substantial socio-demographic and breast cancer characteristic differences among AA and Hispanic populations compared to Caucasians, revealing notable ethnic disparities in breast cancer. Despite these variations, our findings highlight promising healthcare equity, with comparable access to surgical and chemotherapy interventions across ethnicities. TNBC demonstrates molecular heterogeneity and a higher prevalence among AA women, contributing to significant racial disparities.

Geographic and racial disparities in bi-specific antibodies trials access for diffuse large B-cell lymphoma.

1525 Background: The trials of bispecific antibodies to treat diffuse large B-cell lymphoma (DLBCL) have increased exponentially. However, there is a geographic limitation to offering these trials and universal access appears to be limited. Here, we investigate the geographical and racial disparities in accessing bispecific antibodies trials for DLBCL. Methods: We searched ClinicalTrials.gov using the terms for DLBCL and bispecific antibodies. A total of 13 out of 51 clinical trials with one or more open sites in the United States (US) were included in this systematic review. 2020 US Census Bureau data was used to obtain data on race and ethnicity. Analysis for this study was performed using SPSS version 26. Results: The majority of the included trials were Phase I (62%) followed by Phase II (23%), and Phase I/II (15%). A total of 885 participants were either enrolled or expected to enroll in these clinical trials. Nine (69%) clinical trials were only open in the US while 4 (31%) clinical trials were open in the US and other countries. The majority of the trials were funded by the pharmaceutical industry 62%. There were 50 unique study sites distributed over 24 states with a 2.4 (1-10) mean number of trials per state and 9.9 (1-39) mean number of sites per trial. Study sites were distributed in 24 different states. Midwestern states had the highest number of trials 28%, followed by Southern 26%, Northeastern 24%, and Western 22%. The highest number of study locations (10) and the highest number of open studies (10) were in California. Twenty-seven states had no open bispecific antibodies trials including three in the Northeast (Maine, Rhode Island, and Vermont), five in the Midwest (Illinois, Indiana, Nebraska, North and South Dakota), eight in the South (Delaware, Virginia, District of Columbia, West Virginia, Mississippi, Arkansas, Louisiana, and Oklahoma), and eleven in the West (Arizona, Colorado, Idaho, New Mexico, Montana, Nevada, Wyoming, Alaska, Hawaii, Oregon, and Washington). Using US Census Bureau data, only 20% of African Americans (AA) (8 349 699 of 41 104 200) lived in a county with a bispecific antibodies trial. There were only five states (21%) with 50% or more of the AA population living in a county with an open bispecific antibodies trial and seven states (29%) with 30-49.9% of their AA county residents. Five states (21%) had less than 10% of the AA population living in a county with an open bispecific antibodies trial. Nine (90%) out of ten states with the highest proportion of AA residents (18.6%-41.4%) have no (five states) or only one clinical trial site (four states). Conclusions: There is significant geographic and racial disparity in accessing bispecific antibodies trials for DLBCL. Strategies should be framed to address the causes of the observed disparities and to improve access to these trials.

Clustering of Social Determinants of Health as an Indicator of Meaningful Subgroups within an African American Population: Application of Latent Class Analysis.

Health disparities between people who are African American (AA) versus their White counterparts have been well established, but disparities among AA people have not. The current study introduces a systematic method to determine subgroups within a sample of AA people based on their social determinants of health. Health screening data collected in the West Side of Chicago, an underserved predominantly AA area, in 2018 were used. Exploratory latent class analysis was used to determine subgroups of participants based on their responses to 16 variables, each pertaining to a specific social determinant of health. Four unique clusters of participants were found, corresponding to those with "many unmet needs", "basic unmet needs", "unmet healthcare needs", and "few unmet needs". The findings support the utility of analytically determining meaningful subgroups among a sample of AA people and their social determinants of health. Understanding the differences within an underserved population may contribute to future interventions to eliminate health disparities.

#365 Dialysis centers performance: socioeconomic and environmental determinants

Abstract Background and Aims Healthcare outcomes in hemodialysis centers are intricately shaped by a myriad of factors extending beyond clinical realms. This study explores the interplay of socioeconomic and environmental determinants on the performance of 7638 hemodialysis centers in the United States during 2022. Leveraging data from the Centers for Medicare &amp; Medicaid Services, the United States Census Bureau, and the National Center for Environmental Information, our analysis encompasses outcomes like mortality, hospitalization, readmission rates, and emergency department visit rates. Method A dataset comprising information from 7638 US hemodialysis centers, spanning January to December 2022, was obtained through the Centers for Medicare &amp; Medicaid Services, US Census Bureau and environmental data, and from the National Center for Environmental Information. The study assessed mortality, hospitalization, readmission, and emergency department visits within one-month post-hospitalization. Independent variables included dialysis center characteristics, state-specific socioeconomic and environmental data, analysed through descriptive statistics and a linear regression model. Results Results reveal a significant correlation between racial composition and outcomes, with states having higher Latino populations exhibiting lower ED visit rates, contrasting with elevated mortality rates in states with higher African American populations. Socioeconomic factors, such as education and insurance status, influence ED visit rates. Environmental determinants, specifically average yearly state temperature, impact mortality and hospitalization rates. Operational characteristics matter: for-profit centres and those providing higher number of hemodialysis bed correlate with decreased mortality rates, while centres offering peritoneal dialysis or late-shift services demonstrate lower emergency department visit rates. Conclusion Our study unveils a nuanced interplay of factors influencing outcomes in hemodialysis centers. Disparities rooted in race and socioeconomic status underscore the need for targeted interventions. Environmental considerations further contribute to the complexity, while operational characteristics reveal intriguing trends, challenging conventional expectations. This analysis provides a foundation for tailored strategies to enhance the performance and equity of hemodialysis centers.

#2213 APOL1 high-risk genotype in in a Dutch multi-ethnic population

Abstract Background and Aims The presence of 2 APOL1 high-risk alleles (high-risk APOL1 genotype) is associated with an increased risk of ESKD. In the USA, the prevalence of these high-risk alleles is high in people of West African descent and almost absent in patients from European descent. In Amsterdam, there is a significant number of people from Surinam, and (West-) Africa. A big group of Surinamese individuals have a West African heritage. The prevalence, however, of high-risk APOL1 genotype in the Netherlands and thereby the significance is unknown. The aim of this research was to investigate the prevalence of the APOL1 risk alleles in a multi-ethnic cohort of the Amsterdam general population consisting of individuals of African Surinamese, Ghanaian, Moroccan and Dutch origin. Second we correlate the presence of these risk alleles to blood pressure, kidney function and proteinuria. Method HELIUS is a multi-ethnic prospective cohort study including people aged 18-70 who were randomly selected, stratified by ethnic origin, from the Amsterdam general population. Baseline examination took place tween 2011 and 2015. We analysed a population of 5971 individuals with available genotype data, of whom 1287 were of Dutch, 3048 of Moroccan, 1156 of African Suriname and 480 of Ghanaian descent. APOL1 risk was determined by genotyping two APOL1 missense variants, rs73885319A&amp;gt;G, S342G; rs60910145T&amp;gt;G, I384M, together constitute the G1 high-risk allele and the 6-base pair deletion allele, rs71785313 RRRATAA/−, N388Y399/−−, is the G2 high risk allele. Logistic regression analyses were performed to determine correlation between creatinine, eGFR, and systolic blood pressure and apol1 high risk genotype, with additional adjustments for age, sex, and BMI. Results The prevalence of high-risk APOL1 genotype was 4.17% in the total sample, in African Surinamese 9.5%, and in the Ghanaian 29.0%. There were no individuals with high risk genotype in the Moroccan or Dutch descent population. The presence of high risk APOL1 genotype was associated with an elevated creatinine level of 10.68 µmol/L (SD 0.91) in the whole cohort. Also, in the Surinamese and Ghanaian populations population the presence of the high-risk APOL1 genotype was associated with an increased creatinine of 2.6 µmol/L (SD 1.00) as compared to the black population with low-risk APOL1 genotype. People with high-risk APOL1 genotype had significantly higher systolic blood pressure 10.69 mmHg (SD 0.091) than those without. Nevertheless, there was no significant difference in systolic blood pressure in the black population with high-risk APOL1 genotype in comparison with the black population with low-risk APOL1 genotype 1.38 mmHg (SD 1.17). Also, there was no significant difference in eGFR (CKD CKD-EPI 2009) in any analysis and no differences in proteinuria was seen, between those with and without the high-risk APOL1 genotype. Conclusion In this population, the overall prevalence of the APOL1 risk alleles seems to conform to the African American population in the USA. There is however a much higher prevalence of high-risk APOL1 genotype in the Ghanaian in comparison to the African Surinamese. The group with high-risk APOL1 genotype had significantly higher creatinine levels and higher systolic blood pressure. However there was no significant difference in blood pressure within the black population between APOL1 high-risk genotype and low-risk genotype. There was no significant difference in eGFR, possibly because the CKD-EPI 2009 formula was used which overestimates the eGFR in the black population. Better calculation with cysteine C possibly gives different outcomes. In conclusion, this is the first study in Europe investigating the prevalence of APOL1 high-risk genotype in a large population-based cohort. APOL1 risk alleles, and high-risk genotype, are prevalent in our population of African descent. More analysis in this cohort are pending and also longitudinal data will follow.

Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment.

African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.

Increased IgD and CD27 Double Negative (DN) B cell population in pediatric onset autoimmune hepatitis

Autoimmune hepatitis (AIH) is a chronic, inflammatory liver disease of unknown aetiology which requires lifelong immunosuppression. Most therapeutic and outcome studies of AIH have been conducted predominantly in Caucasian (European Ancestry, EA) cohorts, with the exclusion of African American (AA) patients due to inadequate sample size. It is known that AA patients have a severe phenotype of autoimmune diseases and demonstrate a poor response to conventional medical therapy. Understanding cellular and molecular pathways which determine AIH severity and progression in AA patients is likely to lead to the discovery of novel, personalised and better tolerated therapies. The aim of the study is to determine the distinct effector B cell phenotypes which contribute to disease severity and progression of AIH in AA children as compared to their EA cohorts. PBMCs were isolated from blood samples collected from patients visiting Children’s Healthcare of Atlanta (CHOA) and were grouped into AA, (n = 12), EA, (n = 11) and controls (n = 12) and were processed for flow cytometry. Markers of B cell development, maturation and activation were assessed namely CD19, CD21, IgD, CD27, CD38, CD11c, CD24, CD138. AA children with AIH demonstrated an expansion of CD19 + ve, Activated Naïve (aN), (CD19+ IgD-/CD27- Double Negative (DN2) ([CD19+/IgD-/CD27++CD38++) cells. Plasmablasts were significantly higher along with Signalling Lymphocytic activation molecule F7 (SLAMF7). Unswitched memory [CD19+] IgD+CD27+ (USM) B cells were significantly contracted in AA patients with AIH. B cell phenotyping reveals a distinct profile in AA AIH patients with a major skewing towards the expansion of effector pathways which have been previously characterised in severe SLE in AA patients. These results suggest that the quantification and therapeutic target of B cell pathway could contribute substantially to the clinical approach to AIH especially in the AA population.

The Value of Adding Exosome-Based Prostate Intelliscore to Multiparametric Magnetic Resonance Imaging in Prostate Biopsy: A Retrospective Analysis

Introduction: Currently, there is limited evidence for the relationship of Exosome-based Prostate Intelliscore (EPI) and multiparametric magnetic resonance imaging (mpMRI) in stratifying risk for clinically significant prostate cancer. Using a retrospective cohort study design, we sought to characterize the relationship between these two noninvasive metrics and prostate biopsy outcome. Methods: Data were collected via electronic medical record for all patients who underwent EPI testing from 1 January 2019 to 3 February 2022 and had available medical records at a single mid-western university medical center. Positive test result was defined as &gt;15.6 for EPI, ≥3 PI-RADS score and ≥3 + 4 Gleason Score for biopsy findings. Utility of EPI, mpMRI and combined use was characterized through calculation of sensitivity, specificity, positive predictive value, negative predictive value, and ROC analysis. Results: A total of 226 patients were identified as receiving EPI testing for risk stratification of clinically significant prostate cancer. Sensitivity for EPI was 91%, mpMRI was 90%, and the highest was combined use at 96%. With ROC analysis, AUC for EPI alone was 0.57 (95% CI, 0.47–0.67) and 0.78 (95% CI, 0.70–0.87) for mpMRI alone. With prior positive EPI result, AUC for combined use with mpMRI was 0.80 (95% CI, 0.71–0.89). Further subgroup analysis resulted in increased AUC values of EPI 0.67 (95% CI, 0.48–0.87), mpMRI 0.90 (95% CI, 0.76–1.0), and combined 0.90 (95% CI, 0.75–1.0) in the African American population. Discussion: We observed that the combined use of EPI and mpMRI led to an avoided biopsy in 43% of patients. Using both parameters increased the overall sensitivity and diagnostic accuracy in detecting clinically significant prostate cancer. The best test performance was observed in the African American cohort. Identifying optimal noninvasive tools to assess risk for prostate cancer is crucial to providing accurate and cost-effective care. Future study should utilize a prospective study design to further support the combined use of these metrics.

Venous Thromboembolism in Patients Diagnosed with Coronavirus Disease 2019

Background Coronavirus disease 2019 (Covid-19) infection is associated with an increased risk of venous thromboembolism (VTE). However, it is unclear if mild Covid-19 infection is a significant risk factor for VTE. Our goal was to investigate the overall incidence of VTE in Covid-19 patients at our community hospital and assess its correlates. Methods We retrospectively reviewed the medical records of patients 18 years and older who tested positive for Covid-19 at our hospital between March 2020 and September 2021. Results A total of 5926 patients aged 18 to 99 years had Covid-19. Of these patients, 64 (incidence of 1.08%) had VTE; 63% were male and 58% were African Americans. The highest rate of VTE was seen in patients with cardiovascular risk factors (n=47, 73%) followed by a history of thromboembolism (n=19, 30%); patients (n=6, 9%) with mild Covid-19 also developed VTE. Conclusions In our study of a predominantly African American population, the VTE incidence (1.08%) was ten times higher than the general population’s rate of 0.1%. Covid-19 infection, even mild category, not requiring hospitalization was a risk factor for VTE. The risk was increased in men and those who have cardiovascular risk factors and/or prior history of thromboembolism.

Disparities in Multiple Myeloma Mortality Rate Trends by Demographic Status in the USA.

Multiple myeloma (MM) is a hematological malignancy that arises when plasma cells undergo malignant monoclonal proliferation. This study aimed to assess the demographic disparities and temporal trends in the mortality rates of this disease. We employed the Center for Disease Control and Prevention's Wide-ranging ONline Data for Epidemiologic Research (CDC WONDER) database. We found that for the overall U.S. population, the age-adjusted mortality rate per 1,000,000 (AAMR) decreased from 1999 to 2020. However, rates differed between demographic groups. In addition, we sought to find a significant average annual percent change (AAPC) in mortality rate from 1999 to 2020 for various demographic populations and compared groups to find disparities in mortality rate trend. In 2020, the AAMR due to MM was 38.0 and for women 24.1. The AAPC in AAMR from 1999 to 2020 in men was -1.0% (95%CI=-1.3 to -0.7) and in women was -1.6% (95%CI=-1.6 to -2.3). A significant difference in trend by sex was found, where women had a higher rate of decline. In 2020, the AAMR for the American Indian or Alaska Native (AI/AN) population was 15.0, the Asian American and Pacific Islander (AAPI) had 14.8, the Black and African American population had an AAMR of 55.6 and the White population had an AAMR of 28.1. The AAPC for the AI/AN population was -2.2% (95%CI=-3.5 to -0.9), for the AAPI population it was -0.9% (95%CI=-1.5 to -0.4), the Black and African American population had -1.5% (95%CI=-2.2 to -0.8) and the AAPC for the White population was -1.1% (95%CI=-1.6 to -0.6). A significant difference in trend of decline was found between the AAPI and Black and African American populations and between the AI/AN and Black and African American populations. When assessing the U.S. by states, the mid-southeast U.S. had the greatest density of the states with high AAMRs. These findings suggest which populations are at increased risk for mortality due to multiple myeloma and where we should apply additional resources and research.

Abstract PO2-28-04: Pregnancy-associated relapse of triple-negative breast cancer

Abstract Introduction: Pregnancy Triple-negative breast cancer(TNMC) is the absence of ER PR and HER2 receptor expression. It constitutes about 15-20% of all breast cancers and is known to be the aggressive form with a high relapse rate (1). Interestingly, it usually affects women aged &amp;lt; 40 and has a low survival rate in African-American females. This case is a typical presentation of a 38-year-old young woman with PMH of T2NO right triple-negative breast cancer diagnosed in 2017 s/p right mastectomy with sentinel LN biopsy, received immunotherapy and chemotherapy, has been cancer-free for two years, and developed metastatic cancer during her pregnancy. In this case, we understand the diagnostic and therapeutic challenges of TNBC during pregnancy. Case: A 38-year-old African American woman, G0, T2NO triple negative invasive ductal carcinoma, underwent a right breast mastectomy and sentinel LN biopsy. She received treatment with (Anti-PD-L1 Antibody) concomitant with weekly paclitaxel and Doxorubicin/Cyclophosphamide (AC) chemotherapy. However, she had a residual 4cm tumor for which she was treated with adjuvant therapy with capecitabine for six months. A repeat Mammogram in 2019 showed no evidence of malignancy. In 2021, the patient was G2P2L1, admitted to the hospital after having a seizure. CT reported cystic/necrotic left parietal lesion mass effect with 8mm right-sided midline shift with metastasis to lungs and abdominal wall. She underwent L parietal craniectomy with resection of the tumor. At 32 weeks of gestation , chemotherapy with carboplatin and paclitaxel was given after her C-section and Gamma knife radiosurgery for metastatic lesions. She developed super refractory seizures, was induced into a coma with therapeutically anesthetic agents, and passed eventually. Discussion: Little literature exists on pregnancy-associated relapse of triple-negative breast cancer and its deterioration. Our patient was in remission for two years and was diagnosed with metastatic cancer during her second pregnancy. John et al., (2018) discussed an interesting association between breastfeeding, parity, and occurrence of TNBC, that there is a two-fold increased risk of developing TNBC with high parity(3 full-term pregnancies) and short-term breastfeeding (&amp;lt; 12 months) (2). Studies have also shown that cancers during or postpartum pregnancy are aggressive with more tumor burden and metastasize to the lungs, liver, and brain, which is consistent with our patient. (3) Conclusion: Pregnancy-associated breast cancer is diagnostically and therapeutically challenging during or in the postpartum period and with a high propensity of the triple-negative type. It requires a multidisciplinary team approach, awareness in the African American population, clinical suspicion of breast mass during pregnancy warrants imaging, and prolonged breastfeeding postpartum. Diagnosis is usually delayed due to pregnancy, and more research is needed on the diagnostic modalities during pregnancy for early treatment initiation. References Almansour NM. Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence. Front Mol Biosci. 2022 Jan 25;9:836417. doi: 10.3389/fmolb.2022.836417. PMID: 35145999; PMCID: PMC8824427. John EM, Hines LM, Phipps AI, et al. Reproductive history, breast-feeding and risk of triple-negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study. International Journal of Cancer. 2018;142(11):2273. doi:10.1002/ijc.31258 Amant F, Deckers S, Van Calsteren K, Loibl S, Halaska M, Brepoels L, et al. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer (2010) 46(18):3158–68. 10.1016/j.ejca.2010.09.010 Citation Format: Vaidarshi Abbagoni. Pregnancy-associated relapse of triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-04.

Abstract PO3-08-04: Prevalence of BRCA1/2 mutations in an underrepresented population of women with breast cancer: Observations from the City of Hope INSPIRE study

Abstract Background: Because African American and Latina women have been less likely to undergo germline testing, it has been difficult to determine the prevalence of hereditary breast and ovarian cancer predisposition in these populations. Here we report the prevalence of BRCA1/2 mutation in patients with a breast cancer diagnosis from City of Hope’s (COH) INSPIRE (Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation) study. Methods: Patients with a history of any stage breast cancer (stage 0-IV), who were seen by a City of Hope physician at the Duarte or Upland campuses, were approached by a clinical research coordinator for participation in an institutional tissue biorepository project. Demographic information included age, race and ethnicity. Patients consent for this IRB-approved study to store tumor specimens for future research use and Invitae germline testing for 155 predisposition genes which is performed at no cost to the patient. Results: From 7/9/20 until 4/2023, 2413 women consented for participation and underwent germline testing. Mutations in BRCA1 were identified in 53 and BRCA2 in 65. Table 1 summarizes the prevalence of BRCA1/2 mutations according to race and ethnicity. Pathogenic variants in BRCA1 were identified in 22/742 (3.0%) of Hispanic women compared to 16/1552 (1.7%) non-Hispanics (p=0.046). BRCA2 mutations were comparable 16/742 (2.2%) Hispanics and 47/1505 (3%) non-Hispanics. Hispanic women with breast cancer were 2.49 times as likely as non-Hispanics to carry a pathogenic germline BRCA1 mutations than BRCA2 (p=0.026) Conclusion: The prevalence of BRCA1/2 mutations in the African American and Latina population is higher than what was observed in White women. These data provide additional support for the recommendation to perform germline testing in all women with breast cancer, regardless of race or ethnicity Prevalence of BRCA 1 and 2 mutations by Self-Reported Race and Ethnicity # Tested BRCA1 BRCA2 BRCA1 or 2 VUS/Negative Race Native American 15 0 1 (6.7%) 1 (6.7%) 14 (93.3%) Pacific Islander 8 0 0 0 8 (100%) Asian 367 5 (1.4%) 11 (3%) 16 (4.4%) 351 (95.6%) Black 136 7 (5.1%) 4 (2.9%) 11 (8.1%) 125 (91.9%) White 1675 37 (2.2%) 44 (2.6%) 81 (4.8%) 1594 (95.2%) Other 86 1 (1.2%) 4 (4.7%) 4* (4.7%) 82 (95.3%) Unknown 126 3 (2.4%) 1 (0.8%) 5 (3.2% 122 (96.8%) TOTAL 2413 53 (2.2%) 65 (2.7%) 117 (4.8%) 2296 (95.2%) Ethnicity Hispanic 742 22(3%) 16 (2.2%) 37* (5%) 705(95%) Non-Hispanic 1552 26(1.7%) 47(3%) 73(4.7%) 1479 (95.3%) Unknown 119 53(2.2%) 2(1.7%) 7(5.9%) 112(94.1%) TOTAL 2413 53(2.2%) 65(2.7%) 7(5.9%) 112(94.2%) * Patient had both BRCA1 and BRCA2 mutations Citation Format: Joanne Mortimer, Sydney Lindsey, Ilana Solomon, Wai Park, Duveen Sturgeon, Kathleen Blazer, Stacy Gray, Joseph Bonner, Xiaoyu Xia, Stephen Gruber. Prevalence of BRCA1/2 mutations in an underrepresented population of women with breast cancer: Observations from the City of Hope INSPIRE study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-04.