African American Black Research Articles

Community-Engaged Approaches for Improving the Inclusion of Diverse Communities in a Nutrition Clinical Trial.

Cardiometabolic disease (CMD) disproportionately affects African American/Black (AA) and Latino communities. CMD disparities are exacerbated by their underrepresentation in clinical trials for CMD treatments including nutritional interventions. The study aimed to (1) form a precision nutrition community consultant panel (PNCCP) representative of Latino and AA communities in Los Angeles to identify barriers and facilitators to recruitment and retention of diverse communities into nutrition clinical trials and (2) develop culturally informed strategies to improve trial diversity. A deliberative community engagement approach was used to form a PNCCP for the Nutrition for Precision Health (NPH) trial, part of the of the All of Us research initiative. The PNCCP included individuals that provide services for Latino and AA communities who met during 11 virtual sessions over 1 year. Discussion topics included enhancing recruitment and cultural acceptance of the NPH trial. We summarized CCP recommendations by theme using an inductive qualitative approach. The PNCCP included 17 adults (35% AA, 47% Latino). Four thematic recommendations emerged: reducing structural barriers to recruitment, the need for recruitment materials to be culturally tailored and participant-centered, community-engaged trial recruitment, and making nutrition trial procedures inclusive and acceptable. We outlined the study response to feedback, including the constraints that limited implementation of suggestions. This study centers community voices regarding the recruitment and retention of AA and Latino communities into a nutrition clinical trial. It highlights the importance of community engagement early on in protocol development and maintaining flexibility to enhance inclusion of diverse communities in nutrition clinical trials.

Disparate Rates of Germline Variants in Cancer Predisposition Genes in African American/Black Compared With Non-Hispanic White Individuals Between 2015 and 2022.

African American/Black (AA/B) individuals are under-represented in genomic databases and thus less likely to receive definitive information from germline genetic testing (GGT) than non-Hispanic White (NHW) individuals. With nearly 500,000 AA/B and NHW individuals having undergone multigene panel testing (MGPT) for hereditary cancer risk at a single commercial laboratory, to our knowledge, we present the largest study to date investigating cancer GGT results in AA/B and NHW individuals. MGPT results from a retrospective cohort of AA/B (n = 48,684) and NHW (n = 444,831) patients were evaluated. Frequencies of pathogenic germline variants (PGVs) and variants of uncertain significance (VUS) were compared between AA/B and NHW individuals. Changes in frequency of VUS over time were determined. Pearson's chi-squared test was used to compare categorical variables among groups. All significance tests were two-tailed, and P < .05 was considered statistically significant. Between 2015 and 2022, rates of VUS decreased 2.3-fold in AA/B and 1.8-fold in NHW individuals; however, frequencies of VUS and PGV remained significantly higher (46% v 32%; P < .0001) and lower (9% v 13%; P < .0001) in AA/B compared with NHW individuals. Rates of VUS in ATM, BRCA1, BRCA2, PALB2, and PMS2 were significantly higher in AA/B compared with NHW individuals, whereas rates of PGV in BRCA1, BRCA2, and PALB2 were higher in AA/B compared with NHW individuals (P < .001). Despite reductions in VUS frequencies over time, disparities in definitive GGT results persist. Increasing inclusion of AA/B populations in both testing and research will further increase knowledge of genetic variants across these racial groups.

Impact of Smoking Cessation Motivations and Barriers on Quit Intentions Following a Hypothetical Flavor Ban Among African American/Black Individuals Who Use Menthol Cigarettes: A Mixed-Methods Study.

The Food and Drug Administration (FDA) has proposed banning cigarettes and cigars with characterizing flavors-products used disproportionately by African American/black (AA/B) individuals. Little is known about how AA/B individuals who smoke menthol cigarettes will respond to flavor bans or how to amplify the intended benefits. This study explored predictors of quit intentions following a hypothetical flavor ban and further probed anticipated ban-related responses. We recruited 213 AA/B individuals who use menthol cigarettes from Richmond, VA (September 2021-August 2022) for a mixed-methods study. Participants rated seven motivations for quitting and six barriers to quitting (Not a motivation or challenge[1]-Major motivation or challenge[4]), then reported how likely they were to quit smoking if characterizing flavors were banned in cigarettes and cigars. A subsample of 31 participants completed semi-structured interviews to further explore reactions to flavor restriction policies. Multivariable linear regressions suggested that participants who were more motivated to quit smoking because of "information about health hazards" and the "cost of cigarettes" reported higher quit intentions following a hypothetical menthol ban (p < .05). Additionally, those with cessation-related weight concerns reported lower post-ban quit intentions (p < .05). Interview themes highlighted smoking for stress reduction, harm/addiction perceptions of flavored tobacco products, trusted sources of tobacco-related information (including testimonials from people who formerly smoked), potential ban responses, and varying experiences with cessation strategies. Culturally specific cessation strategies that emphasize the health-related benefits of quitting, particularly those featuring the experiences of people who formerly smoked, may help AA/B individuals who smoke menthol cigarettes quit following a menthol ban. For the FDA's proposed bans on characterizing flavors in cigarettes and cigars to advance racial health equity, they must maximize cessation among African American/black (AA/B) individuals who use menthol cigarettes. This work suggests information on the health hazards and costs of smoking, as well as concerns over gaining weight, were predictors of quit intentions in a hypothetical flavor ban. Qualitative data suggest messaging highlighting the experiences of individuals who successfully quit may constitute an effective communication strategy. These insights can be used in the development of culturally specific cessation strategies for AA/B individuals who smoke menthol cigarettes.

The impact of race and other demographic factors on the false positive rates of five embedded Performance Validity Tests (PVTs) in a Veteran sample

ABSTRACT Introduction It is common to use normative adjustments based on race to maintain accuracy when interpreting cognitive test results during neuropsychological assessment. However, embedded performance validity tests (PVTs) do not adjust for these racial differences and may result in elevated rates of false positives in African American/Black (AA) samples compared to European American/White (EA) samples. Methods Veterans without Major Neurocognitive Disorder completed an outpatient neuropsychological assessment and were deemed to be performing in a valid manner (e.g., passing both the Test of Memory Malingering Trial 1 (TOMM1) and the Medical Symptom Validity Test (MSVT), (n = 531, EA = 473, AA = 58). Five embedded PVTs were administered to all patients: WAIS-III/IV Processing Speed Index (PSI), Brief Visuospatial Memory Test-Revised: Discrimination Index (BVMT-R), TMT-A (secs), California Verbal Learning Test-II (CVLT-II) Forced Choice, and WAIS-III/IV Digit Span Scaled Score. Individual PVT false positive rates, as well as the rate of failing two or more embedded PVTs, were calculated. Results Failure rates of two embedded PVTs (PSI, TMT-A), and the total number of PVTs failed, were higher in the AA sample. The PSI and TMT-A remained significantly impacted by race after accounting for age, education, sex, and presence of Mild Neurocognitive Disorder. There were PVT failure rates greater than 10% (and considered false positives) in both groups (AA: PSI, TMT-A, and BVMT-R, 12–24%; EA: BVMT-R, 17%). Failing 2 or more PVTs (AA = 9%, EA = 4%) was impacted by education and Mild Neurocognitive Disorder but not by race. Conclusions Individual (timed) PVTs showed higher false positive rates in the AA sample even after accounting for demographic factors and diagnosis of Mild Neurocognitive Disorder. Requiring failure on 2 or more embedded PVTs reduced false positive rates to acceptable levels across both groups (10% or less) and was not significantly influenced by race.

Understanding the unique needs of African American/Black caregivers.

220 Background: A lack of culturally responsive resources, systemic bias in the healthcare system, and a lack of understanding of culture means African American/Black (AAB) caregivers can face additional barriers to providing care. To address this enormous gap, the American Cancer Society (ACS) is leading the charge in the way support is delivered to AAB caregivers through qualitative inquiry to better understand their unique needs and challenges. Methods: Six focus groups with AAB caregivers (n=32) were conducted using the Zoom online platform to assess a) their perceptions of providing care to a person with cancer, b) their unmet needs, and c) their preferences for how best to meet their needs. NVivo 12 was used to store, code, query, and organize the data. Deductive codes were derived based on the research questions for the study. Data was also inductively coded to identify the categories and themes that emerged that did not fit into the research questions. Results: Participants were mostly female (90%), ≥ 55 years old (64%), employed full time (54%), and providing care to their mother with cancer (42%). The primary unmet need was related to their relationship with their loved one’s healthcare providers. Major themes identified: negative healthcare system perceptions, racism and discrimination, limited access to medication due to cost, provider insensitivity and dismissiveness, medical mistrust, and lack of informational resources. Caregivers highlighted the desire for timely information from the provider about the cancer diagnosis to better assist with treatment decisions. Early navigator involvement was also requested to assist them in advocating for the patient’s needs as well as their own. Conclusions: Caregivers are a critical part of the healthcare team. Providers should strive to deliver culturally competent care that acknowledges and respects the experiences, values, and beliefs of AAB caregivers. Themes that emerged from this study were used to develop topics for a 6-part ECHO Series aimed to address AAB caregiver needs at the system level. ACS will leverage these findings to develop information and resources targeted to AAB caregivers.

Abstract P5-03-05: Distinct molecular differences between African American/Black and White women with Triple Negative Breast Cancer

Abstract Introduction: Triple-negative breast cancer (TNBC) is an aggressive disease that lacks well-defined molecular targets. It accounts for 15-20% of all breast cancers and disproportionately affects women of color due to both limited access to treatment and genetic variation. Recent studies identified BRCA1(or 2) and the PIK3CA/AKT1/PTEN axis as targets for treatment, but these studies neglected to account for genetic variations between race. Here, we present molecular differences between African American/Black (AA) and White (W) women with TNBC to highlight the importance of accounting for race to develop effective therapy and improve long-term outcomes. Methods: This study utilized the TCGA Firehose Legacy Breast Carcinoma dataset on cBioPortal. Subjects with breast cancer and negative ER, PR, and HER2 scores were stratified into AA (n=32) and W (n=69) subgroups. Data was analyzed to compare the most altered genes, copy number variation (CNV), and survival rates between the subgroups. The logrank test was used to obtain the hazard rate. The GISTIC2 model was used to assess CNV and G-scores (G; amplitude of aberration x frequency of occurrence). Results: The main genetic differences were in PIK3CA and BRCA1(or 2) genes. PIK3CA was detected as one of the ten most altered genes in TNBC, but this alteration was found in less than 10% of the TNBC cases. Of the 10%, PIK3CA was altered in 19% of W and 9% of AA subgroup. BRCA1(2) were altered in 10%(7%) of W but 0%(3%) of AA. Additionally, structural differences in chromosomes contributed to different survival outcomes. Both groups had co-amplification in 8q, but a significant hazard rate difference (z = 5.32, p &amp;lt; 0.001) was found for the W compared to the AA for the MYC gene. Further, the W had significantly higher amplification at 3q (G = 0.8 in W; 0.45 in AA). It is important to note that the PIK3CA gene lies in the 3q.26 region, meaning this gene is amplified significantly in the W subgroup. The AA group had a significant deletion at 8p.23 (G=0.5 in W; 0.8 in AA). Deletion of 8p causes MYC amplification, a targetable alteration. Conclusion: Our analysis reveals critical differences between AA and W subgroups with TNBC. Thus, it is clear that targeting the PIK3CA or BRCA1(2) gene benefits the W more than the AA population. To alleviate the disproportionate burden that AA women with TNBC face, more effort must be geared to find solutions specific to the AA subgroup. A greater sample size will help determine whether MYC amplification is unique to the AA subgroup, and if so, it could be targeted to improve outcomes of AA women with TNBC. Nevertheless, more data and research is needed to understand causes and decrease the rate of disparate outcomes in patients with TNBC. Citation Format: So Hyeon Park, Roy Khalife, Evan White, Anthony Magliocco. Distinct molecular differences between African American/Black and White women with Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-05.

“You Can Put a Price Tag on Complexion”: Understanding Colorism Among African-Born and African American Black Men in America

ABSTRACT: This study explores how young Black men talk about colorism and identity. Few studies have investigated how men of color make meaning of colorism. Providing an open-arena for dialogue about colorism, we conducted two focus groups to examine the perceptions of colorism among young African American and African-born Black males. One focus group consisted of African-born Black men, the other consisted of African American Black men. Participants were recruited from a public four-year research university in the northwestern region of the US and ranged in age from 18 to 25. Findings indicate that to this day, young African American and African-born Black males are significantly impacted by their skin tone in their pursuit of access and opportunity in society, and just like women of color, skin tone influences their relationships, identity, and social mobility.

“You Can Put a Price Tag on Complexion”: Understanding Colorism Among African-Born and African American Black Men in America

ABSTRACT: This study explores how young Black men talk about colorism and identity. Few studies have investigated how men of color make meaning of colorism. Providing an open-arena for dialogue about colorism, we conducted two focus groups to examine the perceptions of colorism among young African American and African-born Black males. One focus group consisted of African-born Black men, the other consisted of African American Black men. Participants were recruited from a public four-year research university in the northwestern region of the US and ranged in age from 18 to 25. Findings indicate that to this day, young African American and African-born Black males are significantly impacted by their skin tone in their pursuit of access and opportunity in society, and just like women of color, skin tone influences their relationships, identity, and social mobility.

Patient, Caregiver, and Oncologist Experiences With and Perceptions of Racial Bias and Discrimination in Cancer Care Delivery.

Cancer prevention and treatment systems are significantly impacted by interpersonal, organizational, and structural and systemic racism. A wide body of research has found that racial disparities in access to guideline-adherent cancer care are pervasive throughout the United States and contributing factors include social determinants of health, insurance status, and bias and discrimination in care delivery. Although the existence of racial disparities in cancer care and outcomes is well established, there has been limited research exploring the patient and caregiver experience with bias and discrimination in cancer care. Two national surveys were conducted, one of patients and caregivers and one of oncologists. The surveys examined patient and caregiver experiences with and oncologist perceptions of racial disparities in cancer care. The surveys found that when patients and caregivers were asked about negative care experiences, differences across race were observed. Patients and caregivers identifying as African American/Black (AA/B) or Hispanic/Latino (H/L) were more likely to report at least one negative care experience than patients and caregivers identifying as White (W). Patients who were AA/B or H/L were also more likely than W patients to report that the healthcare system treats people unfairly based on their racial or ethnic background and that racial bias occurs often or very often when a patient and doctor are of different racial/ethnic background. A slight majority of oncologists reported that the healthcare system treats people unfairly based on their racial or ethnic background. The survey results highlight a need for improved racial representation in the oncology professional workforce, improved implicit bias training, and improved clinical trial recruitment efforts.

Characteristics and Geographic Variation in Sudden Unexpected Infant Deaths in the District of Columbia.

Sleep-related infant death is a major cause of infant mortality in the United States. In the District of Columbia, infant mortality varies widely among regions (2 to 14 per 1000 live births). The study objectives were to analyze the patient characteristics and related variables to sudden unexpected infant deaths at 2 pediatric emergency department (ED) sites and the geographic patterns of infant deaths and their relationship to social vulnerability. This retrospective cohort study examined infants under 1 year of age presenting with cardiac arrest at 2 ED sites from 2010 to 2020. Analysis showed 81 deaths with a median population age of 75 days (SD, 46 days). The most frequent demographics of deceased patients were African American Black (89%) with Medicaid insurance (63%), born at term gestation (66%), and without comorbidity (60%). The cause of death was most frequently undetermined (32%) and asphyxia (31%). Most cases involved bed-sharing (63%), despite more than half of those cases having a known safe sleep surface available. Infant death location showed that most deaths occurred in areas with the highest social vulnerability index, including near a community ED location. Understanding the etiologies of this geographic variability may enhance sleep-related infant death prevention strategies.

Evolution of a research team: the patient partner perspective

IntroductionDespite a movement toward the inclusion of patient partners or advisors as part of the research team in all funded studies, few publications have discussed patient engagement from the patient partners’ perspective.MethodsQualitative interviews were conducted by independent qualitative researchers to collect and summarize the experiences and perspectives of the 16 Patient Partners (PPs) on the study team for PeRson EmPowered Asthma RElief (PREPARE), a large, pragmatic study of 1200 African American/Black (AA/B) and Hispanic/Latinx (H/L) adults with asthma. This study was funded by the Patient-Centered Outcomes Research Institute.ResultsThis paper, authored by the PPs themselves, summarizes qualitative interview findings. The journey of the PREPARE PPs began with a desire to learn more about asthma and advocate for other individuals with asthma. Many challenges, including intimidation and lack of trust, were overcome as the research team prioritized building a comfortable environment in which PPs’ lived experiences, opinions, and cultural beliefs are valued, and in which PP voices are centered and respected. Over time, the PPs gained confidence in expressing ideas and feedback, and in taking ownership of their role as valued members of the research team. The PP experience has had tremendous personal and professional impact on the PPs themselves, while also modeling a change in the way researchers and PPs relate to and partner with each other.ConclusionThe partnership between PPs and researchers in the PREPARE study has elevated the PP role from external advisors to integral and empowered members of a collective research team, and the partnership developed and evolved over time.

Examination of Race and Autism Intersectionality Among African American/Black Young Adults.

African American/Black (AA/B) young adults with diagnoses of autism spectrum disorders rarely are studied in a way that acknowledges both their racial identity and their autism diagnosis. Little is known about intersectional oppression in the lives of these young adults. Early adulthood is a time when a young people of color may come to terms with a society that may not treat them fairly and equally due to their race. Autistic AA/B young adults may be even more vulnerable to stress and psychological disempowerment due to the added impact of negative experiences of being Black and having an autism diagnosis. Thirty-two autistic and 30 non-autistic AA/B young adults took part in an online survey examining risk factors of everyday discrimination, perceived stress and potential protective factors of psychological empowerment, and Black identity. Differences in score measures for the autistic and non-autistic samples were examined along with the predictors of perceived stress assessed. Frequencies of intersectional discrimination experiences were also examined. Autistic AA/B participants reported significantly less everyday discriminatory experiences than non-autistic AA/B participants, whereas perceived stress was not significantly different between the two groups. The majority of non-autistic AA/B participants endorsed race as their prime source of experiences of discrimination, whereas autistic AA/B participants also cited being autistic as a major contributor to reports of discrimination. Although the autistic group had significantly lower reports of self-determination, they reported higher on the Black identity, private regard scale, pertaining to feelings about group membership, which can be considered a protective factor. There is heterogeneity in reasons for discriminatory experiences for autistic AA/B young adults whereby some of the participants (12%-30%) endorsed race + disability as dual reasons for experiencing regular discrimination. Mental health clinicians and other direct service providers working with autistic AA/B young adults should understand that intersecting identities of race and disability may be at play when they are working with these individuals, and that treatment should consider these factors.

Racial differences in treatment patterns and outcomes of first-line (1L) therapies for advanced renal cell carcinoma (aRCC) in the real-world (RW) setting.

4548 Background: In 1L therapy for aRCC, nivolumab plus ipilimumab (NIVO+IPI) and pembrolizumab plus axitinib (PEM+AXI) have demonstrated significantly improved clinical outcomes versus sunitinib in phase III trials. African American/Black (AA) patients are grossly underrepresented in all aRCC trials. Little is known about the impact of racial differences on the use of 1L therapies and clinical outcomes in the RW setting. Methods: This retrospective chart review included AA and White American (WA) patients diagnosed with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)/Memorial Sloan Kettering Cancer Center (MSKCC) intermediate/poor (I/P)-risk aRCC who initiated on 1L NIVO+IPI, PEM+AXI, or tyrosine kinase inhibitor (TKI) monotherapy with sunitinib, pazopanib, or cabozantinib. Patients’ demographic/clinical characteristics and outcomes were abstracted from medical charts by treating oncologists. Use of 1L therapy, treatment discontinuation, and clinical outcomes including disease response, landmark progression-free survival (PFS), landmark overall survival (OS), and treatment-related adverse event (TRAE) rates were assessed descriptively by race. Results: Of 473 patients, 95 (20.1%) were AA, and 378 (79.9%) were WA patients. Median follow-up was 10.9 months. A higher proportion of AA vs. WA patients had received 1L TKI monotherapy (21.1% vs. 16.1%). Treatment discontinuation rate was higher in AA vs. WA patients (49.5% vs. 43.4%). Treatment response was lower in AA than WA patients (overall response rate [ORR]: 58.8% vs. 74.8%; complete response [CR]: 8.2% vs. 11.4%). The TRAE rate was slightly lower in AA vs. WA patients (25.3% vs. 32.5%). Stratified clinical outcomes including landmark PFS and OS rates at 6 and 9 months are shown in the Table. Conclusions: In this RW I/P-risk aRCC cohort, fewer AA patients were treated with standard of care immune-oncology (IO)-based therapy vs. WA patients, which may contribute to differences in therapy discontinuation and survival outcomes. Also, even with short follow-up, clinically meaningful ORR differences are noted in AA and WA patients. [Table: see text]

Poverty or Racism?: Determinants of Disproportionality and Disparity for African American/Black Children in Child Welfare

For decades, the incessantly tethered over-involvement of African American/Black (AA/BL) families with the U.S. Child Welfare System (CWS) has been uniquely troubling. Child welfare researchers have asserted “poverty” over “racism” as the root determinant of the historical disproportionate overrepresentation of AA/BL children in CWS. This commentary explores the extent this assertion holds once an apples-to-apples comparison of poor AA/BL and WH children in the CWS is examined. Using 2018 and 2019 National Child Abuse and Neglect Data Systems (NCANDS) Child File data, rates of disproportionality and disparity for AA/BL and White (WH) children receiving public assistance (PA) (2018: N = 333,640; 2019: N = 321,273) were computed at two CW decision points [disposition of maltreatment investigation and subsequent services administered]. Among these poor children, AA/BL were found to be disproportionately overrepresented and WH children underrepresented compared to their proportion of the U.S. child population at each decision point. AA/BL children were also found to be three times more likely to have their maltreatment substantiated and subsequently be placed in foster care compared to their WH counterparts. The issues of racial disproportionality and disparities still exists when comparing poor AA/BL to poor WH children, which suggests “racism” is operational at decision points in the U.S. CWS and should not be minimized or omitted as a consequential determinant.

Greater Social Functioning Associated With Lower Depressive Symptomatology Among Black Belt African Americans Enrolled in the Southeastern Collaboration to Improve Blood Pressure Control Study.

Objective: In many populations, higher social functioning is associated with lower depressive symptomatology, which in turn is associated with improved cardiovascular health. This study aimed to establish an association between social functioning and depressive symptomatology, which has not yet been demonstrated in the African American Black Belt. This would be an important finding in a region with high cardiovascular morbidity. Methods: This observational study used baseline data from 1,225 African American Black Belt residents with uncontrolled hypertension in the Southeastern Collaboration to Improve Blood Pressure Control (SEC) trial. Three Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires—the emotional support, instrumental support, and social isolation questionnaires—and marital status assessed social functioning. The 8-item Patient Health Questionnaire assessed depressive symptomatology. Multivariable logistic regression models examined associations between social functioning and depressive symptomatology separately and then simultaneously. Data were collected from May 2017 to April 2021. Results: Social functioning was higher than US-reported averages, and the prevalence of moderate to severe depressive symptomatology was low (20.8%) among primary care populations. In a separate model, lower emotional support, lower instrumental support, and increased social isolation were significantly associated with greater depressive symptomatology (odds ratio = 1.56, 95% CI, 1.20–2.02; OR = 1.33, 95% CI, 1.01–1.77; and OR = 2.39, 95% CI, 1.81–3.16, respectively). In a simultaneous model, only increased perceived social isolation remained significantly associated with greater depressive symptomatology (OR = 2.24, 95% CI, 1.67–3.00). Conclusions: Greater social functioning is associated with lower depressive symptom burden in the Black Belt region. Future research into the directionality of this association could assist in the development of interventions to improve regional mental and cardiovascular health. Trial Registration: ClinicalTrials.gov identifier: NCT02866669

Successfully Reducing Severe Asthma Exacerbations and Improving Asthma Control in a Pragmatic Study in African American/Black (AA/B) and Hispanic/Latinx (H/L) Patients with Moderate-Severe Asthma (PREPARE)

Efforts to reduce the disproportionate asthma morbidity in African American/Black (AA/B) and Hispanic/Latinx (H/L) patients have been mostly unsuccessful. In a pragmatic, randomized study, we tested a Patient-Activated Reliever-Triggered Inhaled Corticosteroid (ICS) Strategy (PARTICS) in 1201 AA/B and H/L patients with moderate-to-severe asthma.

Title: Genomic and Systemic Metabolism Differences Associated with Racial Disparities in Multiple Myeloma

BackgroundRacial disparities exist in the prevalence of multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS), with significantly higher prevalence in African American/ black (AA) compared to non-AA individuals. AA patients are also younger than non-AA at the time of diagnosis. We aimed to determine if differences in systemic metabolism and genetics might contribute to these racial disparities in MM. There are currently no approved anti-myeloma therapeutics that simultaneously reverse the metabolic drivers for MM tumor growth.MethodsStudies were approved by the IRB and IACUC. We used a large health system electronic medical record database to characterize the metabolic phenotype of AA and white individuals with MM. Body mass index (BMI) was calculated from height and weight measures. BMI≥30kg/m 2 defined obesity. HbA1c ≥6.5% defined diabetes. Genomic analysis was performed by extracting mutational signatures from tumor samples of MM patients as previously described (PMID: 23945592), and comparing their prevalence between AA and white patients. We used an immunodeficient non-obese mouse model of type 2 diabetes (Rag1-/-/MKR) and controls (Rag1-/-) for in vivo MM1.S xenograft studies. ON123300, a dual ARK5/CDK4 kinase inhibitor was used for preclinical studies.ResultsOf our population of 3170 people, 2128 individuals were AA (21.7%) or white (78.3%). Females comprised 53.2% (n=246) of the AA population and 40.2% (n=669) of the white population. The highest prevalence of obesity was in AA women (46%) > white men (41%) > AA men (36%) > white women (35%). The prevalence of diabetes was greater in AA men (37%) and women (34%) than white men (24%) and women (19%). BMI was a poor predictor of diabetes in the AA population with MM, where diabetes affected 1 in 5 AA individuals with normal BMI, but only 1 in 12 white individuals.Genomic characterization of AA patients, revealed a significant enrichment for the COSMIC SBS1 clock-like mutational signature in AA patients compared to white (p < 0.05), which was confirmed after adjusting for age. The SBS1 signature correlates with the age of individuals and may represent a cell division clock.The male Rag1-/-/MKR mice had hyperglycemia and insulin resistance, and were not obese relative to control mice when fed a regular chow diet. The MM1.S tumor xenografts grew much more rapidly in the Rag1-/-/MKR mice compared with controls; 60 days post injection, tumors were approximately 5 times larger than controls and ex vivo analysis of protein lysates revealed increased activation of the insulin receptor (IR) / insulin-like growth factor 1 receptor (IGF-1R) and mTOR signaling pathway. Our previous studies (Perumal et al, CCR 2016) have characterized a role for ARK5(AMPK-related protein kinase 5), which is a major regulator of glutamine uptake in tumor cells that co-express ARK5 and MYC. Preclinical testing of MM cell lines and xenograft mouse models show a robust reduction of MM tumor growth as well as inhibition of IGF-1R-downstream signaling pathways, which contribute to tumor proliferation.ConclusionsIn our large diverse cohort of individuals with MM, we found significant racial disparities in the prevalence of obesity and type 2 diabetes, in addition to enrichment of a clock-like mutational signature in MM from AA individuals. Our findings suggest a signature of accelerated aging in MM from AA patients, which is concordant with younger age at diagnosis. In our mouse model, MM xenografts grew more rapidly in the diabetic mice and had more activation of mTOR signaling, a pathway known to regulate clock and aging gene signatures. ON123300 was able to reverse the metabolic drive as well as directly reduce tumor growth in vivo xenograft models. DisclosuresParekh: Foundation Medicine Inc: Consultancy; Amgen: Research Funding; PFIZER: Research Funding; CELGENE: Research Funding; Karyopharm Inv: Research Funding.

P-102: Genomic and systemic metabolism differences associated with racial disparities in Multiple Myeloma

<h3>Background</h3> Racial disparities exist in the prevalence of multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS), with significantly higher prevalence in African American/ black (AA) compared to non-AA individuals. AA patients are also younger than non-AA at the time of diagnosis. We aimed to determine if differences in systemic metabolism and genetics might contribute to these racial disparities in MM. <h3>Methods</h3> Studies were approved by the IRB and IACUC. We used a large health system electronic medical record database to characterize the metabolic phenotype of AA and white individuals with MM. Body mass index (BMI) was calculated from height and weight measures. BMI≥30kg/m2 defined obesity. HbA1c ≥6.5% defined diabetes. Genomic analysis was performed by extracting mutational signatures from tumor samples of MM patients as previously described, and comparing their prevalence between AA and white patients. We used an immunodeficient non-obese mouse model of type 2 diabetes (Rag1-/-/MKR) and controls (Rag1-/-) for in vivo MM1.S xenograft studies. <h3>Results</h3> Of our population of 3170 people, 2128 individuals were AA (21.7%) or white (78.3%). Females comprised 53.2% (n=246) of the AA population and 40.2% (n=669) of the white population. The highest prevalence of obesity was in AA women (46%) > white men (41%) > AA men (36%) > white women (35%). The prevalence of diabetes was greater in AA men (37%) and women (34%) than white men (24%) and women (19%). BMI was a poor predictor of diabetes in the AA population with MM, where diabetes affected 1 in 5 AA individuals with normal BMI, but only 1 in 12 white individuals. Genomic characterization of AA patients, revealed a significant enrichment for the COSMIC SBS1 clock-like mutational signature in AA patients compared to white (p < 0.05), which was confirmed after adjusting for age. The SBS1 signature correlates with the age of individuals and may represent a cell division clock. Our finding suggests accelerated aging in AA MM patients, which is concordant with younger age at diagnosis. The male Rag1-/-/MKR mice had hyperglycemia and insulin resistance, and were not obese relative to control mice when fed a regular chow diet. The MM1.S tumor xenografts grew much more rapidly in the Rag1-/-/MKR mice compared with controls; 60 days post injection, tumors were approximately 5 times larger than controls and ex vivo analysis of protein lysates revealed increased activation of the insulin receptor (IR) / insulin-like growth factor 1 receptor (IGF-1R) and mTOR signaling pathway. <h3>Conclusions</h3> In our large diverse cohort of individuals with MM, we found significant racial disparities in the prevalence of obesity and type 2 diabetes, in addition to enrichment of a clock-like mutational signature in MM from AA individuals. In our mouse model, MM xenografts grew more rapidly in the diabetic mice and had more activation of mTOR signaling, a pathway known to regulate clock and aging gene signatures.

The Black Pacific and the Shapes of Global Black Power

The Black Pacific and the Shapes of Global Black Power

Demographic differences in performance validity test failure

Objective The present study investigated demographic differences in performance validity test (PVT) failure in a Veteran sample. Method Data were extracted from clinical neuropsychological evaluations. Only veterans who identified as men, as either European American/White (EA) or African American/Black (AA) were included (n = 1261). We investigated whether performance on two frequently used PVTs, the Test of Memory Malingering (TOMM), and the Medical Symptom Validity Test (MSVT), differed by age, education, and race using separate logistic regressions. Results Veterans with younger age, less education, and Veterans Affairs (VA) service-connected disability were significantly more likely to fail both PVTs. Race was not a significant predictor of MSVT failure, but AA patients were significantly more likely than EA patients to fail the TOMM. For all significant demographic predictors in the models, effects were small. In a subsample of patients who were given both PVTs (n = 461), the effects of race on performance remained. Conclusions Performance on the TOMM and MSVT differed by age and level of education. Performance on the TOMM differed between EA and AA patients, whereas performance on the MSVT did not. These results suggest that demographic factors may play a small but measurable role in performance on specific PVTs.