AbstractAfrican Americans Research Articles

Abstract LB137: Comparison of HPV virus-induced oropharyngeal cancer by self-reported race and the potential implications on treatment

Abstract African Americans exhibit lower survival rates from Human Papillomavirus (HPV)-induced squamous cell carcinomas in comparison to other population groups. While socioeconomic status and access to healthcare may contribute to these disparities, mounting evidence indicates that significant biological differences between diverse ancestries play a role in the severity of different cancers such as breast cancer, colorectal cancer, and squamous cell carcinomas. The purpose of the study is to investigate diagnostic and biological differences in HPV-induced squamous cell carcinomas of the oropharynx by self-reported race. The study population consists of oropharynx cases identified at the University of Michigan (non-Hispanic White) and through the Louisiana Tumor Registry (African American). A total of 52 individuals from two study sites were included in this study, 40 of whom are men, two are women and 10 are unknown. Forty-four percent (23/52) of individuals were African Americans (AA), and 46 % (19/52) were Non-Hispanic White (NHW). Formalin-fixed paraffin-embedded (FFPE) tumors from these patients were tested for p16 expression via immunohistochemistry as a proxy for HPV status. Fifty-two percent (27/52) tested negative (p16-) and 48% (25/52) tested positive (p16+). Total RNA from these samples was extracted, sequenced, and bioinformatically analyzed to test for the presence of HPV. Among AA samples, 61% were negative for both p16 and HPV RNA (p16-/RNA-), 26% were p16+/RNA-, 13% were p16+/RNA+ and none were p16-/RNA+. Among NHWs, 37% were p16-/RNA-, 16% were p16-/RNA+, 47% were p16+/RNA+ and none were p16+/RNA-. Interestingly, 6 of 20 HPV RNA- AA samples were p16+, whereas 0 of 7 HPV RNA- NHW samples were p16+. We performed data dimensionality reduction using Principal Component Analysis (PCA) implemented in the PCAtools Bioconductor package. Four groups were separated in a plot of the first two PCs, comprising, (i) all p16+/RNA+ (18/18), (ii) dominantly p16-/RNA- (6/7), (iii) p16-/RNA- mixed with p16+/RNA-, and (iv) p16-/RNA+ in the middle of all the groups and mixing with some p16+/RNA+ samples. A total of 13/17 (76%) p16-/RNA- samples in group (iii) that were mixed with p16+/RNA- samples were AA, 3 (18%) were NHW and 1 was unknown. Based on clinical data, the PCA group (iii) consisted of samples that were characterized as invasive, keratinizing, and moderately differentiated, whereas group (ii) samples were mostly clinically characterized as nonkeratinizing. A total of 13/14 AA samples that tested p16-/RNA- possessed similar clinical attributes as samples classified as p16+/RNA-, suggesting that the p16 expression via immunohistochemistry test might be classifying a significant percent of HPV-negative AA samples as positive. Taken together, these results suggest that the p16 immunohistochemistry test for oropharyngeal cancer may be overly sensitive for classifying AA oropharynx cancer samples. Clinical decisions regarding treatment for AA based on this test have the potential to negatively impact outcomes. Citation Format: Batsirai M. Mabvakure, Shiting Li, Deborah de la Caridad Delgado Herrera, William Benjamin, Lucia Martinez Cruz, Siddhi Patil, Elham Mohebbi, Gregory T. Wolf, Anju Duttargi, Christina Lefante, Mei-Chin Hsieh, Nisha J. D'Silva, Maureen Sartor, Laura Rozek. Comparison of HPV virus-induced oropharyngeal cancer by self-reported race and the potential implications on treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB137.

Abstract 7004: DNA Methylation analysis of African American colorectal cancers reveal race-specific alterations

Abstract African Americans (AAs) have among the highest incidence and mortality rates of colorectal cancer (CRC) in the US. They present with more right-sided, microsatellite stable (MSS) tumors and are diagnosed at earlier ages than non-Hispanic Whites (NHW). While DNA methylation changes and their significance have been previously described in CRC, much less is known about the unique DNA methylation changes that occur in AA CRCs compared to NHW CRCs. In the current study, we analyzed DNA methylation changes in AA patients and compared those changes to data from NHWs. AA patients diagnosed with a MSS colorectal tumor at the Yale New Health System were included in the study. A pathologist reviewed archival slides, and selected areas from CRCs (n=160) and adjacent normal tissue (n=42) were cored (median age=59; 82 females, 78 males). DNA was bisulfite converted and analysis performed using EPIC arrays. The 450K methylation array from NHW CRCs was also analyzed for 217 CRCs and 20 normal tissues obtained from TCGA (median age=68; 103 females, 114 males). Differentially methylated regions (DMRs) with |Δβ|>0.1, FDR corrected p-value <0.05 between tumor and normal tissue were identified using SeSAMe. We identified 4881 DMRs (57% hyper- and 44% hypomethylated) between AA CRC and normal tissue. Of these, 46% were in CpG Islands, 15% in CpG Shores, 4% in CpG shelves, and 36% in open sea. Most DMRs (71%) were in promoter regions, with 18% in gene bodies, 5% in enhancer regions, and 6% in intergenic regions. Next, we performed additional DMR analysis using overlapping probes from both arrays to compare NHW with AA data. We identified 2239 DMRs between AA CRC and normal tissue compared to 4138 in NHW. Of the 2239 AA DMRs, 1419 (66%) were common with NHW DMRs, 790 (34%) were unique to AAs. There were many overlapping pathways and genes; however, the DMRs impacting these pathways differed between AA and NHW CRCs. Hypermethylation of LCK, a tyrosine kinase involved in T-cell receptor signaling, was found in 60% of AA CRCs compared to 5.9% of NHW CRCs. LCK hypermethylation leads to CD4/8 T-cell inactivation and linked to poor outcomes in lung cancer. We observed AA-specific hypermethylation of SSTR1 in 57.2% of AA CRCs compared to 27.6% of NHW CRCs. Somatostasin (SST) suppresses tumor growth by regulating certain factors involved in cell proliferation. Hypermethylation of SSTR1 has been associated with various malignancies including gastric cancer. Lastly, promoter hypermethylation of 3 protocadherin genes was found in 65.1% of AAs compared to 33.1% NHWs. Protocadherins regulate WNT signaling and hypermethylation is associated with poor outcomes in multiple cancers. Taken together, these results show AA-specific CRC methylation changes compared with NHW CRCs. Further work is warranted to investigate the potential functional and clinical implications of these methylation alterations, some of which may represent therapeutic targets and biomarkers. Citation Format: Seeta Rajpara, David N. Buckley, Rosa Xicola, Reger Mikaeel, Mary K. Yagle, Baris Kerimoglu, Curtis Thorne, Dante A. Bellomo, Megha Padi, Xavier Llor, Nathan Ellis, Bodour Salhia. DNA Methylation analysis of African American colorectal cancers reveal race-specific alterations [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 7004.

Abstract 6180: Tumor microenvironment phenotypes predict recurrence in African Americans diagnosed with colorectal cancer: A comparative study of manual grading with digital pathology

Abstract African Americans face a higher rate of colorectal cancer (CRC) incidence and mortality compared to other ethnicities. Identifying key prognostic factors is essential for better outcomes in this group. This study focused on the prognostic value of stromal grading in the tumor microenvironment (TME) of African American CRC patients, using both manual grading and digital pathology. A retrospective analysis of CRC cases in African Americans was conducted. Two cohorts were established: a control cohort (patients without recurrence) and a recurrence cohort (patients with recurrence). Stromal grading was performed manually, categorizing tumors into Grade 1 (low risk), Grade 2 (moderate risk), and Grade 3 (high risk), and we also quantified the TME percentages by digital pathology: myxoid, collagen, immune and tumor. In the control cohort (N=40), stromal grading identified 30 Grade 1, 7 Grade 2, and 3 Grade 3 cases. Conversely, the recurrence cohort (N=17) demonstrated a starkly different distribution, with 1 Grade 1, 3 Grade 2, and 13 Grade 3 cases. The Chi-square statistic was notably significant (p<0.0001), indicating a strong association between higher stromal grades and the likelihood of recurrence. By unpaired t-test, high myxoid stroma (p<0.0001), low collagen (p<0.0001), and low tumor (p=0.0002) by digital pathology were associated with recurrence. TME phenotypes are a significant prognostic and recurrence indicator in African American patients with CRC. The marked difference in stromal grades and digital pathology features between the control and recurrence cohorts suggests that higher stromal grades, along with higher myxoid, lower collagen and lower tumor percentages are associated with an increased risk of recurrence. These findings underscore the need for tailored therapeutic strategies and more vigilant surveillance in African American patients exhibiting high-risk TME phenotypes. The efficacy of manual and digital pathology evaluation of the TME also warrants further exploration to enhance prognostic accuracy and treatment personalization. Citation Format: Dongling Wu, Rong Xia, Mouyed Alawad, Lili Lee, Tamas Gonda, Wenqing Cao, Sean Hacking. Tumor microenvironment phenotypes predict recurrence in African Americans diagnosed with colorectal cancer: A comparative study of manual grading with digital pathology [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 6180.

GENETIC VARIANTS ASSOCIATED WITH BLOOD PRESSURE PHENOTYPES IN OLDER ADULTS

Abstract African Americans (AAs) suffer from higher rates of uncontrolled HTN even when receiving commonly prescribed classes of antihypertensive medications. Variation in blood pressure (BP) in older adults is known to be associated with a variety of cardiovascular endpoints, yet our understanding of underlying mechanisms is limited. This study aimed to determine if HTN genetic variants influence blood pressure variation within a population of AA older adults taking antihypertensives. Community-dwelling older adults from the Translational Approaches to Personalized Health (TAPH) cohort were recruited to enroll in a 24-hour ambulatory BP monitoring (ABPM) phenotyping study. The Quant Studio 12-K Flex system was used for genotyping participants for three previously established CACNA1C and CACNB2 genetic risk alleles (rs758173, rs2228645, and rs2357790). 69 participants had ABPM data that passed the minimum 80% successful readings threshold: age=68□6, Female=50.3%, Black=73%, White=21%, and Other=6%. ABPM revealed 50.7% controlled HTN, 27.5% Sustained uncontrolled HTN, 14.5 % White coat uncontrolled HTN and 7.2% Masked uncontrolled HTN. ANOVA and Linear regression models found that the CACNB2 genetic risk allele rs2228645 broadly impacts ABPM Phenotypes (C/C SBP= 120.8+/-12.9 mmHg, C/T SBP= 125.73+/-13.5, and T/T SBP= 140+/-34.8 mmHg, p=0.011), mean awake 24-hour SBP (C/C SBP= 124+/-12.7 mmHg, C/T SBP= 133.5+/-14.8, and T/T SBP= 143.7+/-25.6 mmHg, p=0.012), and mean sleep SBP (C/C SBP= 114+/-16 mmHg, C/T SBP= 125.4+/-15, and T/T SBP= 136+/-50 mmHg, p=0.024). CACNA1C and CACNB2 genetic variants influence blood pressure phenotypes in older AAs. Determining genetic variants that affect antihypertensive effectiveness could lead to improved antihypertensive therapy for individuals with HTN/CVD.

Abstract C060: DNA Methylation analysis of African American colorectal cancers reveal race-specific alterations

Abstract African Americans (AAs) have among the highest incidence and mortality rates of colorectal cancer (CRC) in the US. They present with more right-sided, microsatellite stable tumors and are diagnosed at earlier ages than non-Hispanic Whites (NHW). While DNA methylation changes and their significance have been previously described in CRC, much less is known about the unique DNA methylation changes that occur in AA CRCs compared to NHW CRCs. In the current study, we analyzed DNA methylation changes in AA patients and compared those changes to data from NHWs. AA patients diagnosed with a microsatellite-stable colorectal tumor at the Yale New Health System were included in the study. A pathologist reviewed archival slides, and selected areas from tumor (n=160) and adjacent normal tissue (n=42) were cored. The median age of patients was 59 from 82 females and 78 males. Extracted DNA was bisulfite converted and tested using EPIC arrays. DNA methylation (450K) from NHW CRCs was also analyzed for 217 CRCs and 20 normal tissues obtained from TCGA (median age=70; 114 males, 103 females). Differentially methylated regions (DMRs) with |Db|>0.1, FDR corrected p-value <0.05 between tumor and normal tissue were identified using SeSAMe. We identified 4881 DMRs (57% hyper- and 44% hypomethylated) between AA CRC and normal tissue. Of these, 46% were in CpG Islands, 15% in CpG Shores, 4% in CpG shelves, and 36% in open sea. Most DMRs (71%) were in promoter regions, compared with 18% in gene bodies, 5% in enhancer regions, and 6% in intergenic regions. Next, we performed an additional DMR analysis using overlapping probes from the 450K and EPIC arrays to compare TCGA NHW with Yale AA data. We identified 2290 DMRs between AA CRC and normal tissue compared to 4657 in NHW. Of the 2290 AA DMRs, 1405 (61%) were common with NHW DMRs, 885 (39%) were unique to AAs. There were many overlapping pathways and genes involving metabolic functions, DNA damage response, immune response, and WNT signaling. However, the DMRs impacting these pathways differed between AA and NHW CRCs. Several AA-specific DMRs were associated with immune response and included LCK and GPSM3 genes. Hypermethylation of LCK, a tyrosine kinase involved in T-cell receptor signaling, was found in 60% of AA CRCs compared to 8% of NHW CRCs. LCK hypermethylation leads to CD4/8 T-cell inactivation and is linked to poor outcomes in lung cancer. We also observed AA-specific hypermethylation of GPSM3 in 60% of AA CRCs compared to 18% of NHW CRCs. GPSM3 is associated with CD4/8 T-cell infiltration. Lastly, promoter hypermethylation of 6 protocadherin genes was found in 59% of AAs compared to 20% NHWs. Protocadherins play a role in regulating WNT signaling and hypermethylation has been associated with poor outcomes in multiple cancers. Taken together, these results show AA-specific CRC methylation changes compared with NHW CRCs. Further work is warranted to investigate the potential functional and clinical implications of these methylation alterations, some of which may represent therapeutic targets and biomarkers. Citation Format: David N. Buckley, Rosa Xicola, Mikaeel Reger, Mary K. Yagle, Baris Kerimoglu, Curtis Thorne, Dante Bellomo, Megha Padi, Xavier Llor, Nathan Ellis, Bodour Salhia. DNA Methylation analysis of African American colorectal cancers reveal race-specific alterations [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 C060.

The Boss is Watching: How Monitoring Decisions Hurt Black Workers

Abstract African Americans face shorter employment durations than similar Whites. We hypothesise that employers discriminate in acquiring or acting on ability-relevant information. In our model, monitoring Black, but not White, workers is self-sustaining. New Black hires were more likely fired by previous employers after monitoring. This reduces firms’ beliefs about ability, incentivising discriminatory monitoring. We confirm our predictions that layoffs are initially higher for Black than non-Black workers, but that they converge with seniority and decline more with the Armed Forces Qualification Test for Black workers. Two additional predictions, lower lifetime incomes and longer unemployment durations for Black workers, have known empirical support.

The association between social functioning and health literacy among rural Southeastern African Americans with hypertension.

African Americans living in low socioeconomic circumstances are at high risk of poor health outcomes; this is particularly true for those with hypertension. Many African Americans with chronic hypertension living in the rural impoverished Southeastern USA have low health literacy and are socially isolated. These factors are known to have a negative impact on health outcomes, but it is possible that social support may overcome some of the effect of low health literacy. Since little has been reported about this association, we examined the association between social functioning and health literacy in a rural African American population in the Southeast USA. We used baseline data from participants in the Southeastern Collaboration to Improve Blood Pressure Control, a pragmatic trial that recruited rural African Americans with persistently uncontrolled hypertension and collected survey data. Overall, 33.5% of the 1221 person sample reported social isolation, 26.0% reported low instrumental support, 36.0% reported low emotional support, and 63.4% had inadequate health literacy. All three domains of low social functioning were significantly associated with low health literacy, and this effect was robust to multivariable adjustment for sociodemographics and cognitive functioning for social isolation (adjusted odds ratio 1.62, 95% confidence intervals 1.20-2.20). In conclusion, the majority of this sample living in the NC and AL Black Belt had high social functioning but inadequate health literacy. Tests of interventions to improve social support, especially social isolation, may be warranted to overcome low health literacy in this high-risk rural population.

Abstract IA008: Role of race in accelerating progression of colorectal cancer

Abstract African Americans present earlier in age and have higher incidence and mortality from colorectal cancer (CRC) compared to Whites. Socioeconomic inequality in the US that leads to higher comorbid illness among African Americans is likely a driver. Subsequent biological differences in African Americans include higher risk adenoma precursors that are more often proximally located in the colon, low microstatellite instability prevalence, and deficient immunologic profiles compared to Whites that contribute to cancer progression and outcome. Screening for CRC among African Americans had been recommended by some organizations to commence at age 45 or 40 years due to the observed epidemiology; this was not implemented until the US Preventive Services Task Force recommended CRC screening to commence at age 45 years for all races and ethnicities in 2021.Screening for CRC is one modality of intervention that can eliminate disparities; both colonoscopic and non-invasive screening have been shown to eliminate incidence and mortality differences between African Americans and Whites when using navigation. Recent gains in screening utilization among African Americans compared to Whites might be erased as a result of the COVID-19 pandemic. Navigated non-invasive CRC screening might help the unevenness of preventive services recovery from the pandemic if it can be fully implemented. Citation Format: John M. Carethers. Role of race in accelerating progression of colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr IA008.

Abstract C043: Aberrant mRNA splice variants as novel prognostic biomarkers for tumor aggressiveness and treatment resistance in African American prostate cancer

Abstract African Americans (AAs) have among the highest incidence of prostate cancer (PCa) and mortality attributable to this disease, and AA PCa disparities remains a clinical challenge. Specifically, AAs are 1.6 times more likely to develop PCa, and 2.4 times more likely to die from this disease compared to European Americans (EAs). A number of studies have shown that higher mortality and recurrence rates of PCa in AA men were observed even after adjustment for socioeconomic factors, suggesting that intrinsic biological difference may account for part of the PCa disparities. Our recent genomic study has identified global splicing events as critical drivers for promoting AA and EA PCa disparities. In this study, we utilized population-specific cell lines as in-vitro AA and EA PCa models to evaluate the molecular functions of the aberrant splice variants involved in cancer aggressiveness and drug resistance. Comprehensive functional assays (such as MTT, apoptosis, invasion, kinase activity assays, and western blotting analysis in PCa cells treated with vehicle or small molecule drugs, etc.) were employed to elucidate the functional roles of an oncogenic splice variant, PIK3CD-S, in AA and EA PCa cells in response to drug treatments. Immunohistochemistry and RNAScope assays were performed to examine the expression profile of PIK3CD-L (full length) and PIK3CD-S variants in an independent PCa cohort derived from AA and EA patients. Higher PIK3CD-S/PIK3CD-L expression ratios were detected in AA PCa cell lines and patient specimens. In addition, the functional validations have indicated that the higher PIK3CD-S/PIK3CD-L expression ratio in AA PCa cells potentially contributes to the higher cell proliferative and invasive capacities. By targeting splicing mechanism and/or PI3K isoforms using specific small molecule inhibitors in AA and EA cell models, we further explored the functional mechanisms of these oncogenic splice variants underlying the drug resistance. In conclusion, our molecular mapping/validation and functional analysis suggest that high PIK3CD-S/PIK3CD-L expression profile may contribute to the PCa aggressiveness and treatment resistance in AA PCa, potentially serving as a precision prognostic biomarker and novel drug target in advanced PCa Citation Format: Siyoung Ha, Himali Gujrati, Bi-Dar Wang. Aberrant mRNA splice variants as novel prognostic biomarkers for tumor aggressiveness and treatment resistance in African American prostate cancer [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 C043.

Abstract C056: Prognostic relevance of SUV420H2 (KMT5C) gene expression in clear cell renal cell carcinoma: Implications for patients of African ancestry

Abstract African Americans are second only to Native Americans in having the highest incidence of renal cancer. Despite this statistic, very few studies have examined whether there are racial/ethnic differences in gene and protein expression. Since higher stage/grade ccRCC is uniformly lethal, it is imperative that candidate genes and their corresponding protein products be found that can identify patients across various demographics who are at greater risk of progressing to advanced stage/grade, drug-resistant clear cell renal carcinoma; and that can point to the drivers of ccRCC progression in different demographic groups. Using KIRC (clear cell renal carcinoma) TCGA dataset, we observed that SUV420H2 (KMT5C), a Lysine N-Methyltransferase, is significantly overexpressed in ccRCC (p<1E-12). Moreover, SUV420H2 transcripts were significantly elevated in higher stages and grades (p<.001). Higher SUV420H2 transcripts levels were also correlated with metastasis (p<0.01) and were associated with the more aggressive ccB Renal Csrcinoma phenotype (p<0.001). Overexpression of SUV420H2 was also associated with worst overall patient survival (p<0.0001; HR = 2.05 (1.5151 to 2.79) with a mean survival of 2208 days for the high expression group and 3256 days for the low expression group. Elevated levels were also associated with lower Disease Specific Survival [p<0.0001 HR= 2.7658 (1.8406 to 4.1560)] with a mean survival for the high expression group of 2208 versus 3871 days for the low expression group. Significantly shorter progression free disease times [p<0.0001, HR= 1.9830 (1.4389 to 2.7328) were also observed in the higher expression group (2189 days) relative to the low expression group (2971 days). In addition, in silico data analysis revealed that African Americans exhibited higher expression of SUV420H2 transcripts relative to Whites (p=5.94E-09) and that expression was associated with lower survival outcome (p<0.01, HR=4.33 (1.29 to 14.51). Taken collectively, our data suggests that higher levels of SUV420H2(KMT5C) is associated with cancer progression and the more aggressive ccRCC subtypes. Moreover, SUV420H2 behaves in a manner that suggest it may be a possible oncogene and that it is an unfavorable ccRCC biomarker. Analysis of CPTAC database and Human Protein Atlas failed to yield any information of protein expression in relationship to ccRCC. Given that SUV420H2 functions as a histone methyltransferase that specifically trimethylates histone H4, it is possible that dysregulation could result in altered epigenetic processes and inappropriate repression of genes in ccRCC. Lastly, our data underscores the need for proteomics studies that analyze protein expression differences of putative oncogenes or tumor suppressor genes and proteins across racial and ethnic demographic groups. Citation Format: Romonia Renee Reams, Simone Heyliger, Marilyn Saulsbury. Prognostic relevance of SUV420H2 (KMT5C) gene expression in clear cell renal cell carcinoma: Implications for patients of African ancestry [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 C056.

Abstract B037: Effective recruitment strategies utilized in the midst of a COVID-19 pandemic to examine dietary practices and colorectal cancer screening practices of Blacks in New York City

Abstract African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the U.S. Factors that may be contributing to these high rates, however, remain poorly understood. Specifically, this study assessed the relationship between dietary habits and colorectal cancer screening behavior and intent among individuals who identify as Black, with their ethnicity as African-American, Caribbean, and African. There are many factors that influence dietary habits, and a salient factor is culture. Many studies have experienced challenges recruiting in communities of color for various reasons. The purpose of this presentation is to describe recruitment methods utilized for this study in the midst of the COVID-19 pandemic, and to discuss challenges, strategies that were implemented and lessons learned that can inform and improve future recruitment efforts. Effective recruitment strategies included partnership, consistent engagement, and meeting people in places where they frequent and felt comfortable. Utilizing faith-based locations, barbershops, hair salons, and pivotal community locations allowed individuals to trust the researchers, and also eliminated the need to retain study subjects over a period of time, due to on-site data collection. Though our findings are limited to Black families in predominantly minority neighborhoods, we have identified successful strategies for this specific high-risk population and potentially similar others. Citation Format: Cicely K. Johnson, Grace X. Ma, May May Leung, Olorunseun O. Ogunwobi. Effective recruitment strategies utilized in the midst of a COVID-19 pandemic to examine dietary practices and colorectal cancer screening practices of Blacks in New York City [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 B037.

FEASIBILITY OF THE ACTPLAN PROGRAM FOR AFRICAN-AMERICAN DEMENTIA CAREGIVERS: A SELF-DIRECTED MULTIMEDIA DELIVERY

Abstract African Americans (AA) are less likely than White Americans to complete advance care plans or end-of-life treatment documents. They face significantly greater risk of Alzheimer’s Disease, a silent epidemic for this population, and other dementias. The healthcare system’s lack of dementia support for AAs contributes to disparate care. A four-session caregiver group education program was conducted on advance care planning for AA dementia family providers. The program was based on Kolb’s Experiential Learning Model and initially found effective in an R01 study using in-person delivery by a professional. The present pilot assessed feasibility of delivering the program in a self-directed multimedia format without professional facilitation, using Session 1 on tube feeding decisions as the test session. Twenty-six AA dementia caregivers completed the session in groups of 5 to 8 at a church equipped with a large TV screen. On-screen prompts guided navigation through the program which included recorded lecture, slides, short videos on decision-making, and group discussions. Using quantitative and qualitative methods, pre-and post-survey instruments were administered and interviews conducted. Usability ratings averaged 84%. Knowledge and self-efficacy gains exceeded those of the R01, with a 35% increase in correct responses on knowledge items, versus 18% for the R01 subjects; and increase in perceived decisional self-efficacy of 31% versus 30% for the R01 subjects. Qualitative feedback was universally positive. These findings confirm the feasibility of the self-guided multimedia approach to delivery of the program. A large RCT is planned which, if successful, will support wide dissemination to AA caregivers in need.

PHYSICAL ACTIVITY AND EPISODIC MEMORY IN AFRICAN AMERICAN OLDER ADULTS

Abstract African Americans are more likely to have Alzheimer’s Disease (AD) yet less likely to be included in AD research. Additionally, memory complaints may signal the clinical genesis of AD. Interventions such as physical activity that can help individuals maintain their cognitive functioning as they age have merit in research. The objective of this study is to examine the influence of physical activity of various intensities on episodic memory in African American older adults at the interindividual and intraindividual levels over time. We used data from the Health and Retirement Study over 12 years. Our analyses included an indicator of episodic memory and we examined physical activity of three intensities as predictors while controlling for relevant demographic and health variables. Preliminary data indicates that African American older adults who engaged in more frequent physical activity (regardless of intensity) had better episodic memory. Individuals who engaged more frequently in physical activity had a slightly greater rate of decline than those who engaged less frequently in physical activity. Physical activity may act as a buffer against cognitive decline for older adults. Intensity need not be vigorous to observe changes.

BLACK GREEK LETTER ORGANIZATIONS: FACILITATING HEALTH PROMOTION FOR AFRICAN AMERICANS ACROSS THE LIFECOURSE

Abstract African Americans remain underrepresented in accessing and utilizing evidenced-based health promotion interventions (EBIs). Challenges with dissemination and implementation of EBIs further corroborate existing racial/ethnic health/healthcare disparities. Therefore, there is a need to identify effective ways to increase the widespread adoption of health promotion behaviors among African Americans across the life course. It is plausible that engaging in non-traditional partnerships (i.e., community groups or organizations valued in the community with the capacity and infrastructure) could result in greater adoption and improved utilization of EBIs among African Americans. Although frequently overlooked as a study variable in empirically sound public health research, Black Greek Letter Organizations (BGLO) could be an innovative and practical approach to advancing health in the African American community. It is necessary to gain preliminary evidence of feasibility (e.g., motivation, target population reach, acceptability, ). Therefore, the purpose of this study was to conduct a content analysis to identify the intentions and communication trends of BGLOs as it pertains to public health and the African American community and assess population reach and perceptions by evaluating responses to communication specific to health promotion.We assessed health promotion patterns of four BGLOs in a ten-county metropolitan area. Coded content included communication via the organization’s webpage, Facebook, Twitter, YouTube, Instagram, and LinkedIn from a five-year time period. Findings confirm that BLGOs are invested in the health and well-being of the community, place emphasis on mitigating health inequities, and are uniquely positioned to serve as stakeholders for the translation of EBIs to end-users.

BLACK GREEK LETTER ORGANIZATIONS: FACILITATING HEALTH PROMOTION FOR AFRICAN AMERICANS ACROSS THE LIFECOURSE

Abstract African Americans remain underrepresented in accessing and utilizing evidenced-based health promotion interventions (EBIs). Challenges with dissemination and implementation of EBIs further corroborate existing racial/ethnic health/healthcare disparities. Therefore, there is a need to identify effective ways to increase the widespread adoption of health promotion behaviors among African Americans across the life course. It is plausible that engaging in non-traditional partnerships (i.e., community groups or organizations valued in the community with the capacity and infrastructure) could result in greater adoption and improved utilization of EBIs among African Americans. Although frequently overlooked as a study variable in empirically sound public health research, Black Greek Letter Organizations (BGLO) could be an innovative and practical approach to advancing health in the African American community. It is necessary to gain preliminary evidence of feasibility (e.g., motivation, target population reach, acceptability, ). Therefore, the purpose of this study was to conduct a content analysis to identify the intentions and communication trends of BGLOs as it pertains to public health and the African American community and assess population reach and perceptions by evaluating responses to communication specific to health promotion.We assessed health promotion patterns of four BGLOs in a ten-county metropolitan area. Coded content included communication via the organization’s webpage, Facebook, Twitter, YouTube, Instagram, and LinkedIn from a five-year time period. Findings confirm that BLGOs are invested in the health and well-being of the community, place emphasis on mitigating health inequities, and are uniquely positioned to serve as stakeholders for the translation of EBIs to end-users.

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.

Abstract 6265: Do epigenetic outliers impact racial disparities in colorectal cancer

Abstract African Americans (AA) have a higher incidence and mortality rate for colorectal cancer (CRC) compared to Caucasians. DNA methylation profiling on normal colon mucosa from 77 CRC patients and 68 patients without cancer (controls) of AA and Caucasian descent identified a distinct subgroup of CRC patients (11AA and 4 Caucasians) who are statistical “outliers” at a large number of CpGs. Such highly epigenetically disrupted CRC patients are termed “Outlier Methylation Phenotype” (OMP). Comparison of methylome profiles of CRC patients and controls revealed that AA CRC patients have greater disruption of the normal colon methylome than do Caucasian patients. A large fraction of the overall methylation differences found between CRC patients and controls is attributable to OMPs. Estimation of epigenetic ages shows that OMPs have lower epigenetic ages compared to their chronological ages. In other words, OMPs undergo epigenetic age deceleration. Comparison of normal colon mucosa transcription profiles of OMP cancer patients with those of non-OMP cancer patients indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally down-regulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S RDNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with CRC risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections and KRAS mutations. In conclusion, our study suggests a distinct epigenetically disrupted OMP group in CRC that are responsible for disrupted methylome, altered gene expression and microbial dysbiosis. Furthermore, a higher frequency of OMPs among African Americans (11/42) than among Caucasians (5/35) may contribute to observed racial disparities in CRC incidence and outcome. Citation Format: Jayashri Ghosh, Bryant M. Schultz, Joe Chan, Claudia Wultsch, Imad Shureiqi, Stephanie Chow, Ahmet Doymaz, Sophia Varriano, Melissa Driscoll, Jen Muse, Frida E. Kleiman, Konstantinos Krampis, Jean-Pierre J. Issa, Carmen Sapienza. Do epigenetic outliers impact racial disparities in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6265.

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 PO-083: Descriptive pilot study results of belief in research, religious coping, and willingness to participate in clinical trials among African Americans with hematologic malignancies

Abstract African Americans (AAs) are disproportionately affected by certain types of hematologic malignancies. AAs have a 45% higher probability of dying from acute lymphoblastic leukemia and a 12% higher risk of death from acute myeloid leukemia than Hispanics (6%) and non-Hispanic Whites. AAs also present with chronic lymphocytic leukemia at a younger age, have a more advanced stage disease, and lower survival rates in diffuse large B-cell lymphoma and Hodgkin lymphoma compared to non-Hispanic Whites. Despite the efforts of investigators, AAs with hematologic malignancies remain grossly underrepresented in cancer clinical trials. Underrepresentation of this subset of AAs leads to the non-generalizability of clinical trial findings, disparities in cancer treatment outcomes, and survival compared to other minority populations. Even so, few studies have evaluated the underrepresentation of this subgroup of patients in the context of their beliefs and willingness to participate in clinical trials. Yet, the willingness to participate in cancer clinical trials among AAs with solid tumors is well documented. There is also little evidence relating to the moderating effect of religious coping on the association of belief in research and willingness to participate in clinical trials among this subset of patients. Knowing, as well as believing, are essential elements to participating in any clinical trial. Thus, the aims of the descriptive pilot study were to determine if a relationship exists between belief in research and willingness to participate in clinical trials and determine if religious coping moderates the relationship between belief in research and willingness to participate in clinical trials. To address the aims, data on religious coping were captured at one time-point from 31 AAs with leukemia, lymphoma, and multiple myeloma using the validated Brief RCOPE scale and questions that addressed beliefs associated with research and willingness to participate in cancer clinical trials. The results show that there was no statistical difference between belief in research and willingness to participate in clinical trials, and religious coping did not moderate the effect of belief in research on willingness to participate in clinical trials. Statistically significant differences were found between education and belief in research. Participants with less than a high school education had lower belief in research scores than those with some college education, who showed higher belief in research scores. These findings provide preliminary results that suggest future studies are warranted in the study of AAs' beliefs in research. Such studies may contribute to the development of educational interventions to improve the recruitment of AAs with hematologic malignancies into the therapeutic clinical trials for these diseases, with a particular emphasis on educational interventions for those AAs with less than high school education. Citation Format: Marjorie Petty. Descriptive pilot study results of belief in research, religious coping, and willingness to participate in clinical trials among African Americans with hematologic malignancies [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-083.

Feasibility of the ACTPlan Program for African American Dementia Caregivers: A Self-Directed Multimedia Delivery

African Americans (AA) are less likely than White Americans to complete advance care plans or end-of-life treatment documents. They face significantly greater risk of Alzheimer’s Disease, a silent epidemic for this population, and other dementias. The healthcare system’s lack of dementia support for AAs contributes to disparate care. A four-session caregiver group education program was conducted on advance care planning for AA dementia family providers. The program was based on Kolb’s Experiential Learning Model and initially found effective in an R01 study using in-person delivery by a professional. The present pilot assessed feasibility of delivering the program in a self-directed multimedia format without professional facilitation, using Session 1 on tube feeding decisions as the test session. Twenty-six AA dementia caregivers completed the session in groups of 5 to 8 at a church equipped with a large TV screen. On-screen prompts guided navigation through the program which included recorded lecture, slides, short videos on decision-making, and group discussions. Using quantitative and qualitative methods, pre-and post-survey instruments were administered and interviews conducted. Usability ratings averaged 84%. Knowledge and self-efficacy gains exceeded those of the R01, with a 35% increase in correct responses on knowledge items, versus 18% for the R01 subjects; and increase in perceived decisional self-efficacy of 31% versus 30% for the R01 subjects. Qualitative feedback was universally positive. These findings confirm the feasibility of the self-guided multimedia approach to delivery of the program. A large RCT is planned which, if successful, will support wide dissemination to AA caregivers in need.