European American Counterparts Research Articles

Abstract 7060: Mitochondrial metabolism and racial disparity of bladder cancer

Abstract Bladder cancer mortality is significantly higher in African American patients compared to their European American counterparts. This inferior survival of African American cancer patients is driven at least in part by distinctive intrinsic tumor biology, more specifically altered metabolic activity. However, underlying molecular mechanism for the African American bladder cancer mortality are largely unexplored. Our pioneering metabolomic findings demonstrate alterations in metabolic pathways between African American and European American bladder cancer, specifically those involved in driving energy metabolism. Along these line, we observed increased electron transport chain activity and ATP production in African American bladder cancer could be a result of distinctive rewiring of energy metabolism compared to their European American counterparts. We further performed gene set enrichment analysis by mapping metabolites to genes and observed that oxidative phosphorylation pathway was uniquely enriched in African American tumors compared to European American tumors. In addition, from in vitro assays, mitochondrial complex protein and activity were altered in African American bladder cancer. To determine the role of glutamine mediated increased electron transport chain activity and ATP production in African American bladder cancer, we evaluated the metabolic flux using 13C labeled tracers in both African American and European American bladder cancer cell lines. Metabolic flux analysis revealed that African American cell lines are more glutamine dependent and that producing increased tricarboxylic acid intermediates. Overall, our data indicate that elevated mitochondrial metabolism and oxidative phosphorylation driven by enhanced glutaminolysis may facilitate African American bladder cancer progression. These findings provide the rationale to use mitochondrial-specific inhibitors to target at least a subset of African American bladder cancer patients. Citation Format: Karthik Reddy Kami Reddy, Jun Hyoung Park, Roni J. Bollag, Martha K. Terris, Seth P. Lerner, Minhaj Siddiqui, Yair Lotan, Jianjun Gao, Benny Abraham Kaipparettu, Nagireddy Putluri. Mitochondrial metabolism and racial disparity of bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7060.

Abstract 4830: Predicting drug treatment response in African American lung cancer patients who smoke

Abstract Background: Lung cancer is the third most commonly diagnosed cancer in the US and the leading cause of cancer-related death. African Americans (AAs) have higher lung cancer incidence and mortality rates, and lower survival rates, when compared to their European American (EA) counterparts. It is widely known that cigarette smoking is the strongest risk factor for lung cancer development, but it also plays a significant role in clinical outcome. Cigarette smoking after lung cancer diagnosis (up to 30% patients) comes with several risks, including increased secondary tumors and mortality rates (by 20%), as well as poor treatment outcomes (higher radiation and chemotherapy failure and higher drug clearance). There are limited transcriptomic studies that describe molecular characterizations of AA smokers with lung cancer to predict treatment outcomes. Hypothesis: Cigarette smoking leads to greater drug resistance-related gene expression in AA lung cancer patients. Methods: mRNA expression changes in an AA (NCI-H2172) and EA (NCI-H1944) lung cancer cell line pair exposed to liquid cigarette smoke condensate (CSC) were profiled. The cell lines were matched based on age (62 years), sex (female), histology (lung adenocarcinoma, LUAD, the most common subtype), and culture properties (adherent). The CSC was derived from Murty Pharmaceuticals and prepared by smoking University of Kentucky's 3R4F Standard Research Cigarette on an FTC Smoke Machine. A total of 500,000 cells per well were treated for one hour under standard incubation conditions (37°C, pH 7.0, 5% CO2). Cells were pelleted, RNAs were isolated, treated with DNAse-I to remove contaminating genomic DNA, quantified, and sent for bulk mRNA-sequencing (Novogene Co). Three biological replicates and technical triplicates were performed. Partek Flow and Partek Genomics Suite workflows were used to identify population-specific differentially expressed gene (DEG) signatures and pathway enrichment after CSC exposure. DEG were profiled in LUAD tissues from current smokers in an AA and EA TCGA cohort (n = 18 AAs, 86 EAs). Results: Population-specific gene expression changes were discovered (n = 52 AA DEGs, n = 31 EA DEGs; P <0.001). All of the DEGs were mutually exclusive with no overlap. Some pathways were shared between both populations and others were unique. PI3K/Akt/mTOR signaling pathway enrichment was unique in AA LUAD cells and ECM receptor interactions were distinct in EA LUAD cells. AKT2 (which activates mTOR) had significantly higher expression in LUAD tumor tissues from current AA smokers compared to current EA smokers. Conclusion: Population-specific PI3K/Akt/mTOR pathway alterations may help explain drug resistance in LUAD tumors from AA patients. PI3K signaling is considered a significant cause of resistance to chemotherapy, targeted therapy, and immunotherapy. Future Directions: Expose AA and EA LUAD cell lines to CSC and PI3K/Akt/mTOR pathway inhibitors. Citation Format: Mia Ray, Isaiah Osei-Gyening, Kwabena Acheampong, Marisa Riebesell, Khadijah A. Mitchell. Predicting drug treatment response in African American lung cancer patients who smoke [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4830.

They have a point: Testing strategies to improve receptivity to interracial criticism and promote behavioral change

People tend to be more resistant to criticism of their own group when it is given by outgroup members as opposed to ingroup members because they view the criticism as less constructive and legitimate when delivered by an outsider—a phenomenon known as the intergroup sensitivity effect, or ISE. The present study (N = 827) examines the effectiveness of two rhetorical techniques—balanced criticism (delivering criticism of one’s own group in addition to the target group) and buttering up (delivering praise alongside criticism) in reducing the ISE among European Americans, African Americans, and Latino Americans. The impact of criticism on intentions to engage in corrective behavior was also explored. Participants read a fictitious interview excerpt containing criticism of their racial group delivered by a racial ingroup or outgroup member and then rated the critic and their statement on several dimensions. We found buttering up reduces the ISE among European Americans and Latino Americans, but not African Americans, while critiquing one’s own racial group alongside the target group is ineffective in reducing the ISE for the three examined groups. Additionally, we found African Americans were more willing to engage in corrective behavior to address criticism directed toward their racial group than their European American or Latino American counterparts. However, contrary to previous research, the group membership of the critic did not affect participants’ willingness to engage in corrective action. These findings contribute to our understanding of interracial dynamics in the United States and illuminate how to facilitate interracial criticism.

Investigation of Formaldehyde Concentration in Indoor and Outdoor Air, A Systematic Review

Formaldehyde, commonly recognized as formalin, stands as the archetypal aldehyde, distinguished by its colorless gaseous form and acrid scent. Widespread usage and dissemination of this compound pose potential risks of dermatological and ocular irritation, respiratory ailments, genetic alterations, and carcinogenesis. This study aims to explore the concentrations of formaldehyde in both indoor and outdoor environments. The search strategy involved querying English-language articles in Google Scholar and Science Direct databases, specifically selecting those detailing formaldehyde concentrations. Ultimately, 16 articles meeting the criteria were included in the study. Results reveal that outdoor formaldehyde mean concentration reached up to 17.02 ± 11.46 ppm, while indoor level was 0.528 ± 0.527 ppm. Industrial settings exhibited the highest concentrations, with a mean of 10.73 ± 4.5 ppm. The study exposes higher formaldehyde levels in Asian countries (0.0522 ± 0.075 ppm) compared to European and North American counterparts. Additionally, concentrations displayed a tendency to rise during the summer (3.57 ± 5.03 ppm) in contrast to the winter season (3.08 ± 5.03 ppm). These findings underscore the need for heightened awareness and regulatory measures to mitigate formaldehyde exposure, especially in industrial contexts and regions with elevated concentrations.

Abstract C002: Integrating multiomics data to identify African ancestry-informative markers acting as eQTLs in breast cancer

Abstract Ancestry-informative markers (AIMs) are SNPs that are found at relatively higher frequencies in a specific population and can be used to estimate genetic ancestry. Genetic ancestry is becoming more commonly used in biomedical research investigating the genetic basis of diseases. For many cancers, the literature suggests that African ancestry is associated with poor response to treatment, poorer prognosis, and poorer survival. More specifically, African American women with breast cancer are more likely to have more aggressive subtypes of the disease and diagnosed with a later stage of the disease at an earlier age compared to their European American counterparts. Some of this disparity remains after accounting for socioeconomic factors, suggesting a genetic basis for the health disparities observed in many cancers. To evaluate the genetic basis of cancer health disparities in populations of African ancestry, we identified a set of 46,787 African ancestry informative markers (AIMs) using 1000 Genomes Project data from African and European populations. These AIMs were functionally annotated and investigated for potential associations with cancer in the literature, using tools such as VEP, SIFT, and Polyphen. Using multiomics data (RNAseq, genotype, methylation, copy number variation) from The Cancer Genome Atlas and an integrative eQTL modeling approach, we are investigating which of these AIMs act as expression quantitative trait loci in breast cancer. Of the 47K SNPs identified, 0.6% percent was found to be in the coding regions of the genome and AIMS located on chromosomes 8, 10, 11, 15, 18, and 19 were found to be associated with different cancers in the literature including breast and colorectal cancers. Approximately 5K of the AIMs were found in the TCGA breast cancer data and preliminary results identified cis-eqtls in 4 different genes including SERINC2 and ZSCAN23, and trans-eqtls in about 8 genes including CLCN3 and DEDD. These eQTL AIMs are being evaluated for potential association with ancestry-specific differential survival and response to treatment in breast cancer. Citation Format: Samantha Boudeau. Integrating multiomics data to identify African ancestry-informative markers acting as eQTLs in breast cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C002.

Abstract B004: Dealing with prostate cancer racial disparity: Galeterone and next-generation galeterone analog VNPP433-3β potently inhibits proliferation of prostate cancer cells from African American patient by degrading AR and Mnk1/2

Abstract Prostate cancer incidence and mortality rates are remarkably higher in African-American (AA) men as compared to their European-American (EA) counterparts even after factoring in socio economic status. The disproportionate incidence of prostate cancer and associated mortality in African men is currently becoming more evident as Several studies have reported significant variations in genetic, molecular, epigenetic, microRNA, and cell signaling pathways in patients of Caucasian and African race. As androgen is implicated in prostate cancer progression and about 90% of the cases are Androgen-dependent, blocking androgen action is an effective strategy in treating prostate cancer. Previously, we reported that galeterone and VNPP433-3β, a next generation galeterone analog potently inhibit metastatic castration resistant prostate cancer of Caucasian origin in vitro and in vivo by degrading AR/AR-V7 and Mnk1/2. Since the prostate cancer patients of African descent express significant levels of AR and Mnk1/2, we investigated the efficacy of galeterone and VNPP433-3β in treating prostate cancer of African men. Cell proliferation assay using the cell lines MDA-PCa 2b and RC77 T/E derived from AA prostate cancer patient demonstrates that galeterone and VNPP433-3β can effectively inhibit prostate cancer of African descent at very low concentration. These cell lines are Androgen-sensitive and further biochemical studies reveal that galeterone and VNPP433-3β degrade AR and Mnk1/2 in RC77 T/E and MDA-PCa 2b cell lines, thereby inhibiting its proliferation. Galeterone and VNPP433-3β significantly decrease the half-life of AR in these cell lines by increasing the rate of ubiquitination and proteasomal degradation of AR. Therefore, galeterone and VNPP433-3β hold significant promise for the clinical management of prostate cancer in patients of African descent Citation Format: Elizabeth Thomas, Retheesh Sulochana Thankan, Puranik Purushottachar, Vincent C.O. Njar. Dealing with prostate cancer racial disparity: Galeterone and next-generation galeterone analog VNPP433-3β potently inhibits proliferation of prostate cancer cells from African American patient by degrading AR and Mnk1/2 [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B004.

Brief report: Revealing the nuance: Examining approaches for research with adolescents who identify with multiple racial/ethnic groups.

Increasing racial/ethnic diversity in the United States calls for methodological approaches that capture participants who identify with multiple racial/ethnic groups. Existing approaches are oriented toward large samples (N > 500); yet, we do not know how effective these approaches are with more common smaller convenience samples. We explored how several approaches were associated with the sample distribution of racial/ethnic groups and ethnic identity using a small convenience sample. In 2017, 320 U.S. adolescents (Mage = 16.04 years, SDage = 1.33; 59% female) responded to an open-ended question regarding their racial/ethnic group(s) in a cross-sectional survey. Seventy-five (23%) adolescents identified with multiple racial/ethnic groups. Remaining adolescents identified solely with the Asian/Hawaiian Native/Pacific Islander (19%), Black/African American (3%), European American (21%), Latinx (34%), or Native American/Alaska Native (<1%) group. Three approaches for adolescents with multiple racial/ethnic groups were employed. Findings indicated that the sample distributions differed across the approaches. The greatest differences were shown for Black/African American, Native American/Alaska Native, and Other Race/Ethnicity groups. Descriptively, ethnic identity also differed across the approaches. For example, multiracial/ethnic adolescents reported greater ethnic identity-exploration than their European American counterparts in one approach than in others. Researchers should carefully consider approaches to research with adolescents who identify with multiple racial/ethnic groups given implications for the literature. This study demonstrates the critical need to further develop approaches for capturing the complexity of race/ethnicity.

Abstract 1904: Somatic copy number alterations and gene expression signatures are associated with aggressive tumor biology in African Americans and European Americans with renal cell carcinoma

Abstract Background: Renal cell carcinoma (RCC) is the deadliest of all urologic cancers in the US. RCC survival is highly dependent on histology. Survival rates range between 55-60% for clear cell RCC (ccRCC) and 80-90% for papillary RCC (pRCC) patients. African Americans (AAs) have lower survival rates when compared to their European American (EA) counterparts for both histologies (ccRCC 67.1 vs 72.6, pRCC 80.5 vs 87.5). RCC survival disparities may be accredited to population differences in tumor biology, such as somatic copy number alteration (SCNA) profiles of tumor suppressor and oncogenes, and differential gene expression signatures with associated cellular pathway dysregulation. SCNAs are the most common structural change in the human genome and ccRCC and pRCC-specific SCNAs have been associated with clinical outcomes. ClearCode34, a 34 gene expression signature, was developed to classify ccRCC tumors into two distinct ccRCC subtypes (ccA and ccB). The ccB subtype is associated with worse survival and features like increased tumor size, grade, and metastasis rates. We hypothesize there are more aggressive tumor biology phenotypes in AA RCC patients compared to their European counterparts. Methods: Comparative genome-wide, chromosomal, and gene SCNA analyses were performed in AA and EA ccRCC and pRCC patients in TCGA using Partek Genomics Suite 7 (1-way ANOVA, P&amp;lt;0.05). Prediction analysis of microarray in R was used to classify ccRCC patients into ccA and ccB subtypes by race based on the ClearCode34 gene expression signature (t-test, P&amp;lt;0.05). Differentially expressed genes (DEGs) between AA and EA patients were identified using Partek Genomics Suite 7 (1-way ANOVA, P&amp;lt;0.05). Gene Set Enrichment Analysis (GSEA) was performed using a pre-ranked gene list (Fold changes &amp;gt;2 or &amp;lt;-2, P&amp;lt;0.01) and two Molecular Signatures Database collections (C6 oncogenic signatures, C7 immunologic signatures). Results: AA-enriched SCNVs were identified on chromosomes 1, 3, 6, 7, and 12 in ccRCC patients, and chromosomes 1, 4, 6, 7, 8, 10, 16 and 20 in pRCC patients. Six cytobands and genes experienced a SCNV across both histologies (1p21.1, 1p21.3, 6p12.1, 6p12.3, 6p21.1, 6q12), BMP5 (on 6p12.1), CD2AP (on 6p12.3), ENPP4 (on 6p21.1), and SLC44A3-AS1 (on 1p21.3). AAs and EAs had significantly different frequencies of ccA (AA 33.9% vs EA 52.2%) and ccB subtypes (AA 66.1% vs EA 47.8%). Unique DEGs were found between AA and EA ccA and ccB patients (131 ccA only, 165 ccB only), which corresponded with up- and down-regulation in kidney cancer with oncogenic KRAS (C6) and various immunologic pathways (C7). Conclusions: Population-specific SCNAs, ccB subtypes, and pathways may help explain differences in RCC tumor biology amongst AA and EA patients. Future Directions: Replicate these findings in the Cooperative Human Tissue Network/Geisinger validation cohort. Citation Format: Samantha Greenberg, Alex Bart, Destiny Ortiz Fernandez, Heinric Williams, Khadijah A. Mitchell. Somatic copy number alterations and gene expression signatures are associated with aggressive tumor biology in African Americans and European Americans with renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1904.

Southeast Asian States Have Their Own Views on the Ukraine War

Southeast Asian States Have Their Own Views on the Ukraine War Jeffrey Reeves (bio) Just as Southeast Asia has emerged as the center of gravity for the countries of the global West's respective Indo-Pacific strategies, so too has the region become a priority area for Western diplomacy on the Russia-Ukraine war. Since the start of the conflict, the United States, in particular, has lobbied Southeast Asian states and the secretariat of the Association of Southeast Asian Nations (ASEAN) to condemn Russia's aggression and to comply with Western sanctions against Moscow. In May 2022, for example, the Biden administration raised the Ukraine war in discussions with Southeast Asian leaders at their summit in Washington and tried to insert language in a joint U.S.-ASEAN vision statement criticizing Russia's militarism, ultimately having to settle instead for more vague language on support for territorial sovereignty and international law.1 Similarly, in 2022, the entire Western cohort of the G-20 pressured then host Indonesia to include language criticizing Russia's invasion in the group's joint statement. According to one European sous-sherpa involved in the statement's drafting, China and India also partially supported this language, which therefore made it possible to include.2 In at least one instance, however, European leaders were unable to bring their Southeast Asian counterparts on side with their criticism of Russia. In a December 2022 joint statement following an EU-ASEAN summit, negotiators failed to draft a common critique of Russia's actions.3 Neither have Western leaders had much success in securing Southeast Asian state support in condemnation of the war at the bilateral level, aside from Singapore, which is unique in the region for its relative acceptance [End Page 55] of Western views on the Ukraine war. Indeed, for all the West's efforts to propagate a distinctly critical narrative of Russia in Southeast Asia, regional media, scholarship, and leadership remain either noncommittal to the idea of Russian censure or sympathetic to what they perceive as Russia's strategic logic. As the Ukraine war passed its one-year anniversary in February 2023, Southeast Asian states were decidedly less interested in the war and in criticizing Russia than before. Although in a March 2022 UN General Assembly resolution eight ASEAN members voted to condemn Russia (Vietnam and Laos abstained), polling now shows that Southeast Asian states lead the world in their disinterest toward the war.4 Large majorities of the public in Thailand (60%) and Malaysia (56%) and sizable numbers in Singapore (44%) and Indonesia (48%) believe that the war is not their business and that their states should not interfere.5 Far from being a region that is sympathetic to Western narratives on the Ukraine war, Southeast Asia stands out for its perceived detachment from the conflict. How can one explain Southeast Asian states' apathy toward the war at a time that stands out in many ways as a high-water mark for Western states' attention? While the diversity within and between Southeast Asian states makes it nearly impossible to answer this question comprehensively in short form, there are several trends and characteristics across the region that provide some degree of insight. First, there is a clear lack of consensus on the origins, strategic direction, and global impact of the Russia-Ukraine war among Southeast Asian states and within ASEAN. Second, most Southeast Asian states remain open to and interested in maintaining economic, political, and social ties with Russia despite Western pressure to limit or restrict engagement. Third, Southeast Asian states are, in general, more cynical about Western intentions toward the war than other states, particularly with respect to Washington's proclivity to use the conflict to justify the further isolation of China and NATO's attempt to use the conflict to expand its influence in Asia. In this essay, the author will draw on polling data, official statements, media, and scholarship from across Southeast Asia to detail regional states' contemporary views on the Ukraine war and demonstrate that Southeast Asian states are generally less concerned about Russia's invasion [End Page 56] of Ukraine than their European and North American counterparts, more critical of the war's...

Exploring the Moderating Role of Ethnic Identity in the Relation Between Peer Stress and Life Satisfaction among Adolescents.

Ethnic identity is a crucial aspect of identity development during adolescence. This study aimed to examine the potential protective effect of ethnic identity in the relation between peer stress and global life satisfaction among adolescents. Data were collected via self-report measures from 417 adolescents (ages 14 to 18, 63.0% girls; 32.6% African American, 32.1% European American, 15.0% Asian American, 10.5% Hispanic or Latinx, 6.6% Biracial or Multiracial, and 0.7% Other) at one public, urban high school. The first model tested ethnic identity as the single moderator in the entire sample, and the moderation effect was not significant. The second model added ethnicity (African American vs. European American) as another moderator, and moderation effects were significant for both moderators. Furthermore, the negative effect of peer stress on life satisfaction was stronger for African American adolescents than European American counterparts. For both racial groups, the negative effect of peer stress on life satisfaction decreased as ethnic identity increased. The third model tested a three-way interaction across peer stress, ethnicity (African American vs. European American), and ethnic identity, which was not significant. The results supported the buffering effect of ethnic identity in the context of peer stress for both African American and European American adolescents, and such effect appears to be more important for protecting African American adolescents' life satisfaction, though these two moderators appear to work independently, rather than interact with each other and the peer stressor. Implications and future directions are discussed.

Abstract IA039: The breast cancer biomarkers as predictors of survival: Do they vary by race and ethnicity?

Abstract Introduction: Racial/ethnic disparities in cancer survival in the United States are well documented, but the underlying biology is not well understood. Compared with European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. Our recent studies were aimed to evaluate trends in survival, by race-ethnicity, for women diagnosed with breast cancer. We uncovered some biological factors underlying this disparity by comparing functional expression and prognostic significance of several biomarkers including master transcriptional regulators of luminal differentiation. Materials &amp; Methods: We used a ML approach to assess a cohort of racially diverse 555 primary BC patients who underwent surgery in Greenville, NC and develop proteomics-based genomics (PbG) signatures. We apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), and GP78. The cross-validated models were developed on a BC pooled dataset of (N= 845) samples (primarily taxane and anthracycline based) and chemotherapy cohort (N=415) including racial disparities. Results: Multiplex multivariate analysis of the association of Kaiso’s subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race. Univariate or multivariate HRs for overall survival, estimated from digital IHC scoring of nuclear antigen, show distinct differences in the magnitude and significance of these biomarkers to predict survival based on race: ESR1 [EA HR 0.47; 95% confidence interval (CI), 0.31–0.72 and AA HR 0.77; 95% CI, 0.48–1.18]; FOXA1 (EA HR 0.38; 95% CI, 0.23–0.63 and AA HR 0.53; 95% CI, 0.31–0.88), and GATA3 (EA HR 0.36; 95% CI, 0.23–0.56; AA HR 0.57; CI, 0.56–1.4). In addition, elevated levels of gp78 in patient breast cancer cells predict poor survival. Moreover, high levels of gp78 are associated with poor outcomes in both ER+ and ER– tumors, and breast cancers expressing elevated amounts of gp78 protein are enriched in gene expression pathways that influence cell cycle, metabolism, receptor-mediated signaling, and cell stress response pathways. Conclusion: Understanding these biomarkers and their downstream regulons will elucidate the intrinsic mechanisms that drive racial disparities in breast cancer survival. These findings identify effective modalities of Kaiso biomarker assessment and uncover unanticipated insights into Kaiso’s role in breast cancer progression. Even within clinically homogeneous tumor groups, regulatory networks that drive mammary luminal differentiation reveal race-specific differences in their association with clinical out- come. Our findings implicate a prominent role for gp78 in tumor progression and offer insights into our understanding of racial differences in breast cancer outcomes. Citation Format: Sandeep K. Singhal, Kevin L. Gardner. The breast cancer biomarkers as predictors of survival: Do they vary by race and ethnicity? [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA039.

EXAMINING THE IMPACT OF HEART DISEASE AND DIABETES ON THE MENTAL HEALTH OF OLDER MINORITY ADULTS

Abstract As the world’s population ages and healthcare costs associated with the care of the elderly rise, it is pertinent to address these concerns. This study examines how older adults’ mental health is affected by chronic medical illnesses. It is hypothesized that minority older adults, on average, have worse mental and physical health outcomes than their majority counterparts. A secondary data analysis of the National Health and Aging Trends Study, revealed that older minority adults experience higher rates of depression than non-minority older adults, as measured by the Patient Health Questionnaire – 2 (PHQ-2). European-Americans significantly differ from African Americans (AA) and Hispanics regarding their level of anxiety, as measured by the Generalized Anxiety Disorder – 2 (GAD-2) measure. AA and Hispanics are significantly more likely to exhibit anxiety than their European-American counterparts. Minority older adults with a higher rate of surgeries are not substantially more likely to be depressed, according to the PHQ-2. Minority older adults who reported having a difficult time falling asleep are considerably more depressed than older minority adults who did not endorse depressive symptomatology on the PHQ-2. Minority older adults who had two or more social supports in their lives have lower levels of anxiety compared to older minority adults who have less than two social supports in their lives. The findings from this study serves as groundwork to promote equity between majority and minority older adults, which will improve their abilities to perform independent activities of daily living successfully.

“A Revolution in Labor”: African Americans and Hybrid Labor Activism in Illinois during the Early Jim Crow Era

“A Revolution in Labor”: African Americans and Hybrid Labor Activism in Illinois during the Early Jim Crow Era

Abstract LB173: AACR President's initiative - 2020 by 2020: Democratizing precision cancer medicine and advancing health equity in the black belt

Abstract African Americans (AA) have higher incidence and mortality rates for several cancer types in comparison to their European American (EA) counterparts. Increasing participation in clinical research and patient registries, related to precision cancer medicine, will significantly improve cancer health equity. Many AA cancer patients are treated in community oncology clinics. Unfortunately, these health systems have limited access to Clinical Laboratory Improvement Amendments (CLIA) next generation sequence (NGS) germline and somatic DNA and RNA testing that are used to inform oncologists on the best treatment and/or clinical trial options for cancer patients. Indeed, AA CLIA NGS sample sets are poorly represented, which could presumably result in incomplete knowledge of genomic variants that could affect their treatment and overall outcomes. Hence, it is crucial to implement CLIA NGS efforts for all cancer patients. To address these disparities, Morehouse School of Medicine has formed the Comprehensive Approach to Reimagine health Equity Solutions (CARhES) consortium with Tuskegee University that has engaged community oncology practices in Alabama and Georgia - two of five Black Belt states. The CARhES consortium aims to implement precision cancer medicine to underserved and underrepresented communities that will improve the standard of cancer care by providing access to CLIA NGS testing, clinical trials, and personalized cancer care. Here we describe the first proof of concept of this approach with community oncology partners, i.e., Grady Health System, Wellstar Health System, Georgia Urology, Midtown Urology, and Maui Memorial Medical Center. At the time of consent, saliva, buccal, and tumor samples were collected from participants. Germline and somatic CLIA NGS was performed, and medical reports were returned to practitioners within 14 days. Prior to the COVID pandemic, the study enrolled over 880 patients with a 88% consent rate (n = 1000) in the first 11months of the program. At the start of the COVID pandemic, recruitment efforts were suspended for four months with a slow restart by June 2020. A decrease in the number of staff, office visits (67% reduction), and increase in COVID cases significantly limited recruitment efforts. During this slowdown, we established and improved eConsenting capabilities, which exist today. Community anxiety, due to the pandemic and SARS-CoV-19 vaccine efforts, resulted in a significant reduction in consent rates (88% to 60%). Nevertheless, this study began in April of 2019 and consented 1,750 participants in less than 2 years. Taken together, our study shows that a community-focused precision medicine approach requires meeting people where they are and providing them with access and understanding the benefit of clinical trial participation. The approximate 2,000 clinically annotated genomic AA datasets will greatly contribute to our understanding of cancer health disparities and among the first steps to democratize precision medicine. This study was funded by the American Association for Cancer Research, The Pelotonia Foundation, the M2Gen Foundation, and the National Cancer Institute (U54CA118638). Citation Format: Latrisha L. Horne, Gabriella M. Oprea-Ilies, Eddie R. Stanley, Carla M. Holloway, Margaret P. Hooker, Amina Isom, Derrick J. Beech, Ana Gaonkar, Shavette Harden, Jeffrey F. Hines, LaTonya Randolph, James K. Bennett, Daniel Canter, Darrell J. Carmen, Pooja Mishra, Giuseppe Del Priore, Roland Matthews, Brian M. Rivers, James W. Lillard. AACR President's initiative - 2020 by 2020: Democratizing precision cancer medicine and advancing health equity in the black belt [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 LB173.

Roles Played by Stress-Induced Pathways in Driving Ethnic Heterogeneity for Inflammatory Skin Diseases.

Immune-mediated skin conditions (IMSCs) are a diverse group of autoimmune diseases associated with significant disease burden. Atopic dermatitis and psoriasis are among the most common IMSCs in the United States and have disproportionate impact on racial and ethnic minorities. African American patients are more likely to develop atopic dermatitis compared to their European American counterparts; and despite lower prevalence of psoriasis among this group, African American patients can suffer from more extensive disease involvement, significant post-inflammatory changes, and a decreased quality of life. While recent studies have been focused on understanding the heterogeneity underlying disease mechanisms and genetic factors at play, little emphasis has been put on the effect of psychosocial or psychological stress on immune pathways, and how these factors contribute to differences in clinical severity, prevalence, and treatment response across ethnic groups. In this review, we explore the heterogeneity of atopic dermatitis and psoriasis between African American and European American patients by summarizing epidemiological studies, addressing potential molecular and environmental factors, with a focus on the intersection between stress and inflammatory pathways.

Repair-Assisted Damage Detection Reveals Biological Disparities in Prostate Cancer between African Americans and European Americans.

Simple SummaryProstate cancer is the most diagnosed cancer among men in the United States. African American men are diagnosed with and succumb to prostate cancer at higher rates than other demographic groups. Previously published works described the biological differences in prostate tumors that may contribute to poorer outcomes in African American men compared to European American men. This study was designed to explore the DNA lesion profiles found in prostate tissues. Using tissue microarrays, we found that prostate tumors from African American patients have more uracil and pyrimidine damage, elevated UNG levels, and reduced XRCC1 levels than European American tumors, which may indicate defects in the base excision repair pathway. In addition, these men had higher UMP and lower expression of folate cycle metabolites, suggesting that metabolic rewiring may also contribute to the dysregulation of base excision repair.African Americans (AA) are two times more likely to be diagnosed with and succumb to prostate cancer (PCa) compared to European Americans (EA). There is mounting evidence that biological differences in these tumors contribute to disparities in patient outcomes. Our goal was to examine the differences in DNA damage in AA and EA prostate tissues. Tissue microarrays with matched tumor-benign adjacent pairs from 77 AA and EA PCa patients were analyzed for abasic sites, oxidative lesions, crosslinks, and uracil content using the Repair Assisted Damage Detection (RADD) assay. Our analysis revealed that AA PCa, overall, have more DNA damage than EA PCa. Increased uracil and pyrimidine lesions occurred in AA tumors, while EA tumors had more oxidative lesions. AA PCa have higher levels of UMP and folate cycle metabolites than their EA counterparts. AA PCa showed higher levels of UNG, the uracil-specific glycosylase, than EA, despite uracil lesions being retained within the genome. AA patients also had lower levels of the base excision repair protein XRCC1. These results indicate dysfunction in the base excision repair pathway in AA tumors. Further, these findings reveal how metabolic rewiring in AA PCa drives biological disparities and identifies a targetable axis for cancer therapeutics.

Abstract P4-07-31: Racial disparities in breast cancer chiefly reside in the lesser-known quadruple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) is a notoriously hard to treat and aggressive breast cancer (BC) subtype. Androgen receptor-positive (AR+) TNBC is characterized by AR overexpression and sensitivity to AR antagonists. In contrast, basal-like TNBC lacking AR expression, also known as quadruple-negative breast cancer (QNBC), is refractory to AR antagonists. Women of African descent are predisposed to TNBC. Moreover, QNBC differences between African American (AA) and European American (EA) patients have been noted, with the former expressing distinct basal and immune signatures and having worse outcomes. Although AR testing is not part of standard BC diagnosis and the QNBC subtype is usually reported as TNBC, QNBC may have distinct biological and clinical characteristics. In this study, we examined the prevalence and clinical characteristics of QNBC.Methods: We immunohistochemically evaluated AR expression in formalin-fixed paraffin-embedded TNBC samples (n=760) from our multi-institutional cohorts across the US and Nigeria. Samples with ≥1% AR-positive nuclei were deemed AR-positive. Descriptive statistics were generated for clinicopathological characteristics. Kaplan-Meier (KM) survival analyses were performed to compare overall survival (OS) between patient groups with a different AR status. Multivariable Cox regression analysis was conducted to select the covariates (a≥0.20 removal criterion). AR mRNA levels in patients with BC were evaluated using RNA-seq data retrieved from The Cancer Genome Atlas (TCGA). The Cancer Proteome Atlas (TCPA) BRCA dataset was used to assess AR protein levels.Results: We found an association between African ancestry and AR loss. QNBC accounted for 92.1% of BCs in Africans, 82.4% in AAs, and only 39.8% in EAs. Similarly, analyses of RNA-seq data from TCGA revealed that tumors in AAs with TNBC (n=32) had lower AR mRNA levels than their EA counterparts (n=67). Consistently, AR protein levels in TNBC tumors were lower in AAs than in EAs. Univariate analyses revealed a significant association between QNBC status and high tumor grade (grade 3: 83.02% vs. 66.41%, p&amp;lt;0.001) and high expression of the proliferation marker Ki-67 (≥14%: 85.41 vs. 75.51%, p=0.022) in patients from our multi-institutional cohorts. Race-wise associations showed a non-significant trend of QNBCs in AAs toward higher tumor grade (85.65% vs. 80.27%, p=0.196) and Ki67 expression levels (87.77% vs. 81.06%, p=0.113) compared with QNBCs in EAs. Compared with EAs with QNBC, a higher proportion of AAs with QNBC aged ≤56 (59.17% AAs vs. 45.7 EAs, p=0.011) and had tumors &amp;gt;2 cm (60.88% AAs vs. 45.65% EAs, p=0.075). KM survival analyses indicated that patients with QNBC had worse outcomes than those with TNBC, with significant differences in women of African descent (p&amp;lt;0.05). Furthermore, a race-wise comparison uncovered that while AA and EA patients with TNBC displayed similar OS, AAs with QNBCs had worse OS than their EA counterparts (p=0.03). Finally, we stratified samples in the TCGA BC dataset (n=920) according to AR mRNA levels into AR-low (n=243) and AR-high groups (n=677) and found that among patients in the AR-low subgroup, AAs (n=90) had significantly worse OS than EAs (n=153; p=0.008). No significant differences in OS were observed within the AR-high group (p=0.93).Conclusion: Our findings suggest a strong association between AR loss and African descent. These data offer compelling evidence to support that racial BC disparities in the US lie within the QNBC subgroup rather than the TNBC subtype. These findings also suggest that the widening BC mortality gap between AAs and EAs essentially whittles down to a failure to characterize the QNBC subtype. Citation Format: Shristi Bhattarai, Geetanjali Saini, Manali Rupji, Justin Luningham, Ravi C. Turaga, Uma Krishnamurti, Xiaoxian (Bill) Li, Johnson Agboola, Murtala Abubakar, Haruna A. Nggada, Abidemi Omonisi, Saad A. Ahmed, Luciane Cavalli, Ritu Aneja. Racial disparities in breast cancer chiefly reside in the lesser-known quadruple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-31.

Abstract PO-146: Copy number landscape of primary African-American and European-American prostate tumors

Abstract African-American (AA) men are more likely to be diagnosed with and to die of prostate cancer than their European-American counterparts. Much of this disparity is due to access to care and social determinants of health; however, there is emerging evidence of molecular differences in prostate tumors arising in patients of different genetic ancestry. We investigated the copy number landscape of 290 grade and race-matched primary prostate tumors through interrogation of Infinium MethylationEPIC Array (Illumina) data derived from primary prostate tumors at radical prostatectomy. Our cohort was composed of 145 self-identified AA patients and 145 self-identified EA surgically-treated patients with accompanying genetic ancestry estimation via SNP array (GSAv3). EPIC array-derived copy number data estimated through the Conumee package on R was significantly correlated with genomic losses and gains identified by exome sequencing of a panel with 100 cancer driver genes. We also observed a significant association between genomic losses of the PTEN gene and PTEN protein loss by immunohistochemistry (P&amp;lt;0.001). Similar observations were made for p53 protein nuclear accumulation detected by immunohistochemistry and TP53 gene copy loss (P&amp;lt;0.001). Next, we derived percent genome altered (PGA) from EPIC array data for our 290 patients. PGA from EPIC array was significantly correlated with PGA obtained from targeted sequencing of a subset of AA tumors (n=119, P&amp;lt;0.0001, R²=0.50). No difference in PGA was found between self-identified AA and EA patients (P&amp;lt;0.05), though PGA levels were significantly associated with Gleason Grade groups for both AA (P&amp;lt;0.0001) and EA (P=0.003). We then used the genetic ancestry estimation derived from SNP arrays to identify regions of genomic loss and gain differing by percent African ancestry. We used a comprehensive genome annotation with &amp;gt;80k coding and non-coding regions from FANTOM CAT. Adjusted LIMMA models with age, Gleason Grade Group, and pre-operative PSA levels showed significant copy number differences by percent African ancestry in chromosomes 6p, 10q, 11p, 12p, and 17p. PTEN losses (as expected) and WT1 gains were more frequent in patients with lower percent African ancestry. Gene expression data from TCGA data showed that WT1 expression was significantly increased for self-identified EA patients. Multivariable Cox regression models adjusted for age, Gleason Grade Group, and pre-operative PSA levels revealed that chromosome 8q gains (including MYC, GRHL2, and FZD6) were significantly associated with biochemical recurrence and metastasis. However, when we stratified the models by self-identified race, only AA tumors showed significant associations with 8q gains and poor outcome. Further in silico and mechanistic validation will be conducted to confirm whether chromosome 8 gains may be a potential biomarker for prostate cancer outcome in AA men. Citation Format: Thiago Vidotto, Eddie Imada, Farzana Faizal, Siqun Zheng, Jianfeng Xu, Karen S. Sfanos, Luigi Marchionni, Tamara L. Lotan. Copy number landscape of primary African-American and European-American prostate tumors [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-146.

Abstract 2529: Specific racial CYP2R1 correlation with circadian rhythm genes in prostate adenocarcinoma

Abstract Introduction: Vitamin D in its hormonal form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) binds to the vitamin D receptor (VDR) to regulate genes, for example, in skeletal mineralization. However, it also has other potent biological functions in regulating apoptosis, proliferation, and inflammation. In carcinogenesis, 1,25(OH)2D3 may be exploited to regulate these crucial pathways. It is also clear that a frequent cancer disparity exists amongst African American (AA) men with prostate cancer compared to European Americans (EA). AA men show a higher incidence rate and two to three times increased risk of mortality than EA counterparts. Various groups have suggested that 1,25(OH)2D3 levels and/or VDR functions are risk factors linked with increased prostate cancer incidence in AA men. Incidentally, reports showed that VD plays a crucial role in regulating circadian rhythm (CR). There is, therefore, a need to understand and evaluate 1,25(OH)2D3-dependent CR regulation and the association with racial disparity in prostate cancer. This study aimed to determine if there are differentially expressed VD metabolic enzymes in AA and EA and evaluate if the differential expression correlates with CR genes. Methods: The Cancer Genome Atlas Research Network (TCGA), 2015 database was queried for expression of VD metabolizing enzymes and CR genes. The search was carried out on prostate adenocarcinoma expressions of AA and EA. VD metabolizing enzymes queried are CYP2R1, CYP24A1, CYP27B1, CYP27A1, while CR genes queried include ARNTL, CLOCK, CRY1, CRY2, CSNK1E, NPAS2, PER1, PER2, PER3, and TIMELESS. Prostate adenocarcinoma racial differential expressions of AA and EA were evaluated, and a correlation study was done using the Pearson correlation. Results: VD metabolic enzyme, CYP2R1, and CR gene, ARNTL were significantly upregulated in AA compared to EA counterparts. Although CYPR1 correlates negatively with CLOCK, CRY2, and PER3 in both races, CYPR1 specifically showed a positive correlation with CR gene CRY1 in EA and negative correlations with CR genes NPAS2 and CSNK1E in AA. However, a significant correlation between CYP2R1 and ARNTL in EA and AA was not observed. Conclusion: The data suggest a relationship between racial influence and prostate cancer associated with VD metabolism and CR regulation. Hence, it is crucial to elucidate CYP2R1 regulation in prostate cancer related to VD levels and CR regulation, especially with a focus on racial disparities. Citation Format: Isaacson Bababode Adelani, Solomon Oladapo Rotimi, Clayton Yates, Moray Campbell. Specific racial CYP2R1 correlation with circadian rhythm genes in prostate adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2529.

Directive Guidance as a Cultural Practice for Learning by Chinese-Heritage Babies

We provide a framework of analysis for Chinese ways of learning that extends beyond the individual level. The theoretical framework focuses on Confucian principles of xiào (孝, filial piety), guăn (管, to govern), and dào dé guān (道德觀, virtues), which leads us to argue that directive guidance as a cultural practice nourishes Chinese-heritage children’s learning as early as in infancy. To illustrate how directive guidance occurs in action for infants, we present an empirical study that examined the interaction of mother-infant dyads in Taipei, Taiwan, when they played with a challenging toy. The dyads co-enacted directive guidance more frequently than their European-American counterparts in the USA – through hand holding, intervening, and collaboration – while infants actively participate in the practice. We discuss the early development of strengths for learning that is fostered through culturally meaningful practices recurrent in parent-infant interaction.