non-Hispanic White Individuals Research Articles

Cardiac autonomic function in young healthy Hispanic/Latino adults

The Hispanic/Latino (H/La) population in the US experiences a notably high incidence of hypertension. Recent epidemiological findings reveal that more than 50% of H/La men over the age of 20 years suffer from high blood pressure. Even among adolescents aged 8 to 17 years, H/La youth exhibit the highest prevalence of hypertension compared to other racial groups. This significantly elevates the risk of cardiovascular diseases across the lifespan of this population. H/La is the largest ethnic minority in the US, constituting 19.1% of the current population, and is projected to make up 1/3rd of the US population by 2050. As such, it is crucial to study the potential mechanism responsible for the health disparities in this population. In this study, we investigated the cardiac autonomic function by assessing the baroreflex sensitivity (BRS) and heart rate variability (HRV) in young, healthy H/La and non-Hispanic white (NHW) individuals. We hypothesized that the cardiac autonomic function (BRS and HRV) will be impaired in young healthy H/La as compared to the healthy NHW adults. Ten minutes of resting beat-to-beat blood pressure (BP; finger plethysmography) and heart rate (ECG) were measured in 14 young healthy H/La adults (11 men, 3 women) and 14 age-, sex- and weight-matched NHW adults [age (H/La: 20 ± 2yr; NHW: 22 ± 4yr; mean ± SD, p=0.32); BMI (H/La: 24 ± 2 kg/m2; NHW: 24 ± 2 kg/m2; p = 0.92); positive family history of hypertension (H/La: 21.4%; NHW: 21.4%). The resting heart rate (H/La = 59 ± 5 bpm; NHW = 55 ± 6 bpm; p = 0.12), systolic BP (H/La = 107 ± 6 mmHg; NHW = 111 ± 6 mmHg; p = 0.14) and diastolic BP (H/La = 61 ± 5 mmHg; NHW = 63 ± 6 mmHg; p = 0.46) were similar in both the groups. The respiratory rate (H/La = 14 ± 3 bpm; NHW = 14 ± 3 bpm; p = 0.41) and the sample data used (H/La = 591 ± 59 beats; NHW = 554 ± 63 beats; p = 0.12) for both the populations were similar. We found that BRS (overall gain; H/La = 24 ± 6 ms/mmHg; NHW = 27 ± 10 ms/mmHg; p = 0.39) and heart rate variability (root mean square of successive differences between normal heart beats; RMSSD, H/La = 82 ± 29 ms; NHW = 102 ± 48 ms; p = 0.101) were not significantly different between the two groups. These data suggest that baroreflex sensitivity and heart rate variability are not different between young, healthy H/La and NHW adults. Supported by Kinesiology and Health Education UT Austin Start-up Account 19-2635-91. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex differences in forearm blood flow and vascular conductance responses to rhythmic handgrip exercise in young, healthy Hispanic/Latino adults

Hispanic individuals represent the largest ethnic minority in the United States and are projected to make up one-third of the U.S. population by 2060. Compared to non-Hispanic White (NHW) individuals, Hispanic adults exhibit a significantly higher prevalence of type 2 diabetes (17.9% in Hispanic men vs. 11.5% in NHW men and 14.6% in Hispanic women compared to 7.7% in NHW women). Consequently, Hispanic adults also experience a higher prevalence of other microvascular complications such as neuropathy, retinopathy, and nephropathy leading to end stage renal disease. The underlying mechanisms for this disproportionately high incidence of cardiovascular complications in Hispanic population remains largely unexamined. Previous studies indicate that vascular alterations may manifest early on in life in populations with high cardiovascular disease risk. To date, no study has investigated the differences in vascular function between healthy Hispanic men and women during exercise. Therefore, we tested the hypothesis that Hispanic women (HW) would exhibit greater relative increases in forearm blood flow (FBF) and vascular conductance (FVC) during rhythmic handgrip exercise compared to age-matched Hispanic men (HM). FBF (duplex Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured in 20 young, healthy Hispanic individuals (9 men, 11 women) during rhythmic handgrip exercise performed at three workloads (15%, 30%, and 45% of maximal voluntary contraction (MVC)). FVC was calculated as FBF/MAP. Baseline MAP (HM: 84 ± 5, HW: 85 ± 6 mmHg; p = 0.68) were similar between groups while baseline FBF (HM: 79.23 ± 21.43 and HW: 50.17 ± 28.33 ml/min; mean ± SD, p =0.02); FVC (HM: 0.95 ± 0.27 and HW: 0.60 ± 0.36 ml/min/mmHg; p =0.03); and MVCs (HM: 73.63 ± 18.14 and HW: 52.20 ± 10.73 kg; p < 0.001) were different between Hispanic men and women. Both groups exhibited intensity-dependent increases in FBF and FVC, [(mixed-model two-way ANOVA; %Δ FBF: sex effect p = 0.094, intensity effect p < 0.001, interaction p = 0.247) and (%Δ FVC: sex effect p = 0.032, intensity effect p < 0.001, interaction p = 0.14)]. For example, in response to 45% rhythmic hand grip intensity, there were no differences between Hispanic men and women, %Δ FBF (HM: 465.57 ± 98, HW: 527.27 ± 153.20; p = 0.32) and %Δ FVC (HM: 385.22 ± 65.32, HW: 455.90 ± 132.98; p = 0.17). Change in MAP from baseline to 45% rhythmic handgrip was similar between both groups ( p = 0.67). These preliminary data suggest that Hispanic men and women have similar hyperemic responses to rhythmic handgrip exercise at increasing intensities. Supported by Kinesiology and Health Education UT Austin Start-up Account 19-2635-91. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dementia Prevalence, Incidence and Mortality Trends Among US Adults Ages 72 and Older, 2011-2021.

U.S.-focused studies have reported decreasing dementia prevalence in recent decades, but have not yet focused on the implications of the COVID-19 pandemic for trends. We use the 2011-2021 National Health and Aging Trends Study (N=48,065) to examine dementia prevalence, incidence and mortality trends among adults ages 72 and older, and the contribution to prevalence trends of changes in the distribution of characteristics of the older population ("compositional shifts") during the full and pre-pandemic periods. To minimize classification error, individuals must meet dementia criteria for two consecutive rounds. The prevalence of probable dementia declined from 11.9% in 2011 to 9.2% in 2019 and 8.2% in 2021 (3.1% average annual decline). Declines over the 2011-2021 period were concentrated among those ages 80-89 and non-Hispanic White individuals. Declines in dementia incidence were stronger for the 2011-2021 period than for the pre-pandemic period while mortality among those with dementia rose sharply with the onset of the COVID-19 pandemic. Shifts in the composition of the older population accounted for a smaller fraction of the decline over the full period (28%) than over the pre-pandemic period (45%). Declines in dementia prevalence continued into years marked by onset of the COVID-19 pandemic, along with declines in incidence and sharp increases in mortality among those with dementia. However, declines are no longer largely attributable to compositional changes in the older population. Continued tracking of dementia prevalence, incidence and mortality among those with and without dementia is needed to understand long-run consequences of the pandemic.

Sarcopenia Identification Using Alternative Vertebral Landmarks in Individuals with Lung Cancer.

(1)Sarcopenia, or low skeletal mass index (SMI), contributes to higher lung cancer mortality. The SMI at third lumbar vertebrae (L3) is the reference standard for body composition analysis. However, there is a need to explore the validity of alternative landmarks in this population. We compared the agreement of sarcopenia identification at the first lumbar (L1) and second lumbar (L2) to L3 in non-Hispanic Black (NHB) and White (NHW) individuals with lung cancer. (2)This retrospective, cross-sectional study included 214 NHB and NHW adults with lung cancer. CT scans were analyzed to calculate the SMI at L1, L2, and L3. T-tests, chi-square, Pearson's correlation, Cohen's kappa, sensitivity, and specificity analysis were used. (3)Subjects presented with a mean age of 68.4 ± 9.9 years and BMI of 26.3 ± 6.0 kg/m2. Sarcopenia prevalence varied from 19.6% at L1 to 39.7% at L3. Cohen's kappa coefficient was 0.46 for L1 and 0.64 for L2, indicating weak and moderate agreement for the identification of sarcopenia compared to L3. (4)Sarcopenia prevalence varied greatly depending on the vertebral landmark used for assessment. Using L2 or L1 alone resulted in a 16.8% and 23.8% misclassification of sarcopenia in this cohort of individuals with lung cancer.

Digital Health Interventions for Cancer Prevention Among Racial and Ethnic MinorityGroups in the United States: A Scoping Review.

The COVID-19 pandemic abruptly accelerated the use of digital health for cancer care. Previously, researchers identified a variety of digital health interventions for cancer prevention. The purpose of the present scoping review was to identify digital health interventions for cancer prevention designed for racial/ethnic minoritygroups. The scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews and was guided by the Arksey and O'Malley methodological framework. A search of PubMed, Ovid MEDLINE, and CINAHL for peer-reviewed research articles published from database inception to August 21, 2023, was conducted. Peer-reviewed studies published in English that employed digital health interventions for cancer prevention, that were conducted among racial/ethnic minoritygroups, and thatwere conducted in the United States were included. Also included were cancer prevention interventions for people who did not have cancer, people who did have cancer, and cancer survivors. Excluded were interventions that included non-Hispanic White individuals, interventions performed outside the United States, interventions that combined face-to-face methods with digital strategies, and interventions that did not clearly include digital health. Articles that focused on technologies for collecting and transmitting health data (e.g., remote patient monitoring) without an explicit tie-in to cancer prevention intervention outcomes were also excluded. Following screening, eight articles met the eligibility criteria. Six of the articles were published prior to the COVID-19 pandemic, and two were published during it. The digital health interventions for cancer prevention in racial/ethnic minoritygroups included screening (n = 5), emotional support and education (n = 1), human papillomavirus vaccination (n = 1), and education and treatment (n = 1). A consistently measured outcome was intervention efficacy. Four authors explicitly stated that theories or theoretical constructs were employed to guide intervention development. Also, no interventions were created using novel devices such as emerging technologies. We identified several notable gaps regarding digital health for cancer prevention among racial/ethnic minoritygroups. Addressing these gaps may help guide continued innovation in the use of digital health for cancer prevention among racial/ethnic minoritygroups.

Trends in Oral Tongue Cancer Incidence in the US

Oral tongue cancer (OTC) incidence has increased rapidly among young (<50 years) non-Hispanic White individuals in the US during the past 2 decades; however, it is unknown if age-associated trajectories have persisted. To examine US trends in OTC incidence and project future case burden. This cross-sectional analysis of OTC incidence trends used the US Cancer Statistics Public Use Database, which covers approximately 98% of the US population, and included individuals with an OTC diagnosis reported to US cancer registries between January 1, 2001, and December 31, 2019. Sex, race and ethnicity, and age. Estimated average annual percentage change in OTC incidence from 2001 to 2019. Given the substantial incidence rate increases among non-Hispanic White individuals compared with those of racial and ethnic minority groups, subsequent analyses were restricted to non-Hispanic White individuals. Forecasted OTC incidence trends and case burden among non-Hispanic White individuals to 2034. There were 58 661 new cases of OTC identified between 2001 and 2019. Male individuals (57.6%), non-Hispanic White individuals (83.7%), those aged 60 years or older (58.0%), and individuals with localized stage disease at diagnosis (62.7%) comprised most cases. OTC incidence increased across all age, sex, and racial and ethnic groups, with marked increases observed among non-Hispanic White individuals (2.9% per year; 95% CI, 2.2%-3.7%). Increases among female individuals aged 50 to 59 years were most notable and significantly outpaced increases among younger non-Hispanic White female individuals (4.8% per year [95% CI, 4.1%-5.4%] vs 3.3% per year [95% CI, 2.7%-3.8%]). While all non-Hispanic White birth cohorts from 1925 to 1980 saw sustained increases, rates stabilized among female individuals born after 1980. Should trends continue, the burden of new OTC cases among non-Hispanic White individuals in the US is projected to shift more toward older individuals (from 33.1% to 49.3% among individuals aged 70 years or older) and female individuals (86% case increase vs 62% among male individuals). The results of this cross-sectional study suggest that the period of rapidly increasing OTC incidence among younger non-Hispanic White female individuals in the US is tempering and giving way to greater increases among older female individuals, suggesting a birth cohort effect may have been associated with previously observed trends. Recent increases among non-Hispanic White individuals 50 years or older of both sexes have matched or outpaced younger age groups. Continuing increases among older individuals, particularly female individuals, may be associated with a shift in the OTC patient profile over time.

The dynamic and reciprocal relationship between perceived everyday discrimination and cognitive function in later life

Objectives This study, based on socioemotional selectivity theory and cognitive theory, investigates the dynamic and reciprocal relationship between perceived discrimination and cognitive function in later life. Methods Data were drawn from four waves of the Health and Retirement Study (HRS 2006, 2010, 2014, and 2018). A total of 4,125 people who were 51 and older were included. Cognitive function was measured by the telephone interview for cognitive status (TICS-27). Perceived discrimination was measured using scores of the perceived everyday discrimination scale. Random intercept cross-lagged panel model (RI-CLPM) was utilized. The model was adjusted for a range of covariates. Subgroup analysis by ethnoracial groups was conducted. Results Cross-sectionally, while lower cognitive function was associated with higher perceived discrimination, this relationship was unidirectional. Longitudinally, higher perceived discrimination predicted lower cognitive function in later waves only among non-Hispanic White individuals. Conclusion Results suggested that a decline in cognitive function may precede and contribute to the worsening of perceived discrimination, which may result in further decline in cognitive function. Lifetime experience of discrimination was discussed as a possible source of the racial/ethnic variations in the relationship. Further study is needed to examine whether this relationship holds among people with cognitive impairment and dementia.

334 Identification of novel plasma protein biomarkers for diagnosis and prediction of Alzheimer’s disease in African Americans

OBJECTIVES/GOALS: To identify novel panel of plasma protein biomarkers to improve prediction and diagnosis of Alzheimer’s disease (AD) for African Americans (AA), who are at greater risk of developing AD compared to non-Hispanic White individuals but are underrepresented in AD research. METHODS/STUDY POPULATION: Pre-existing plasma samples from 460 AA individuals with clinical diagnoses of AD, cognitively unimpaired (CU), mild cognitive impairment (MCI), or dementia with Lewy bodies (DLB) will undergo untargeted proteomics using the SomaScan assay, where modified single stranded DNA aptamers bind to protein targets which are quantified by DNA microarray. Protein expression levels will be compared between diagnostic groups to identify differentially expressed proteins. Additional clinical, genetic, and lifestyle factors will be compared with protein expression when available. Proteins of interest, identified by differential protein expression analysis results, will be included in receiver operating characteristic analyses to identify the optimal set of proteins for diagnostic classification. RESULTS/ANTICIPATED RESULTS: A pilot experiment utilizing plasma from 40 individuals identified multiple differentially expressed proteins (DEPs) between AD and non-AD groups. Eight proteins were nominated from the differential protein analysis into a receiver operating characteristic (ROC) analysis based on pvalue and previous implication in AD genome wide association studies. Proteins involved in microglial activation, neuronal adhesion, cell proliferation, and innate immunity were nominated. The ROC model achieved 100% classification accuracy of AD and CU groups using age, sex, and the eight nominated proteins. It is expected that there will be more significant associations when utilizing the full cohort of 460 AA and that DEPs between AD, CU, MCI, and DLB will be identified. DISCUSSION/SIGNIFICANCE: The nomination of a novel panel of plasma biomarkers developed from an AA cohort will directly serve the AA community by improving access to an early and accurate diagnosis of AD. Access to improved prediction and diagnosis will likely improve disease management, thus improving patient outcomes and decreasing burden on families and caregivers.

A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval= 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.

Abstract 843: The burden of Merkel cell carcinoma attributable to immunosuppression, ultraviolet radiation, and Merkel cell polyomavirus in the United States

Abstract Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. No published study has estimated the contribution of the major potentially modifiable risk factors, such as immunosuppression, ultraviolet radiation (UVR) and infection with Merkel cell polyomavirus (MCPyV), to the burden of MCC in the US. We estimated the population attributable fractions (PAFs) for MCC associated with immunosuppression (HIV and organ transplantation), MCPyV, and UVR in the US during 2001-2020. Methods: We calculated PAFs for immunosuppression and UVR using the formula: prevalence in cases (Pc)*[(Relative risk, RR-1)/RR]. The proportion of MCC cases among organ recipients and people with HIV (Pc) were derived from US cancer registries in the HIV/AIDS Cancer Match Study, Transplant Cancer Match Study, and the Surveillance Epidemiology and End Results (SEER) Program data. To approximate the RRs, we calculated standardized incidence ratios (SIRs) comparing MCC incidence in people with HIV and organ recipients to the general population. We merged SEER data on MCC cases by county with data on ambient UVR levels in order to create population quintiles of UVR exposure. Since only non-Hispanic White individuals showed elevated IRRs for increased ambient UVR exposure, we estimated the PAF of UVR by calculating incidence rate ratios (IRR ≈ RR) comparing MCC incidence in non-Hispanic White individuals to all other races/ethnicities (at any UVR level) as the reference; here, Pc was the proportion of non-Hispanic White patients in each quintile. To estimate the PAF of MCPyV, we meta-analyzed US studies reporting on MCPyV prevalence in MCC tissues (here PAF ≈ Pc). Results: Over the study period (2001-2020), 40,571 MCCs were diagnosed in the US. Compared to the general population, organ recipients had 13 times higher (SIR=12.7, CI: 11.3-14.2) and people with HIV had three times higher (SIR=2.78, CI: 2.01-3.75) risk of MCC. Due to the rarity of these exposures (HIV Pc = 0.4%; Transplant Pc = 1.9%), only 0.2% of MCC cases were attributable to HIV and 1.7% were attributable to organ transplantation. Compared with people in other racial/ethnic groups, the IRRs of non-Hispanic White individuals at the various levels of ambient UVR for MCC arising on the head and neck ranged from 4.24 to 5.03 and for other primary sites ranged from 2.81 to 3.36. After combining the PAFs for these sites, the overall PAF for UVR was 65.8%. Meta-analyzing 20 studies with 984 MCC cases combined, we found that 66.1% (CI: 58.0-72.2%) of MCCs were attributable to MCPyV. Conclusions: While a small proportion of MCCs were due to immunosuppression from HIV infection and organ transplantation, UVR and MCPyV played a major role in MCC burden. Future research is required to assess the combined impact of these risk factors on MCC incidence. Citation Format: Jacob T. Tribble, Karena Volesky-Avellaneda, Qianlai Luo, Michael R. Sargen, Isaac Brownell, Elizabeth K. Cahoon, Meredith Shiels, Ruth Pfeiffer, Adrianne Moreno, Brenda Y. Hernandez, Eric Engels. The burden of Merkel cell carcinoma attributable to immunosuppression, ultraviolet radiation, and Merkel cell polyomavirus in the United States [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 843.

Abstract 7649: Inflammatory biomarkers by sarcopenia status in diverse individuals with lung cancer

Abstract Background: Sarcopenia and inflammation are independent prognostic indicators of poor survival in lung cancer. Systemic inflammation contributes to sarcopenia or low muscle mass through increased catabolism and decreased synthesis of muscle protein. In turn, sarcopenia leads to inflammation in the muscle and exacerbation of systemic inflammation. Specific Aim: The aim of this study was to determine the association between sarcopenia and systemic biomarkers of inflammation including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and albumin in diverse individuals with lung cancer and determine their use as prognostic indicators of sarcopenia. Methods: This retrospective cross-sectional study included 218 non-Hispanic Black (n=111) and White (n=107) individuals with lung cancer. Computed tomography scans were analyzed to calculate skeletal mass index (SMI) at the third lumbar vertebra. Sarcopenia was defined using published sex-specific criteria for SMI in healthy individuals then categorized into the binary variable of sarcopenia/no sarcopenia. NLR, PLR, and albumin were analyzed as both continuous and categorical variables, with NLR&amp;gt; 3, PLR &amp;gt;150, and albumin &amp;lt;3.5 defining moderate to high inflammation. T-tests, Mann Whitney U, Chi square, and adjusted Logistic Regression were used as appropriate. Results: Subjects presented with a mean age of 68.5 + 9.8 years, BMI of 26.3 + 5.9 kg/m2, 50.9% non-Hispanic Black, and 49.5% female with significantly higher prevalence of late-stage lung cancer (61.9% versus 38.1% early-stage, p&amp;lt;0.001) and no differences in age and BMI by race/ethnicity. Mean NLR (6.2 + 7.2), PLR (226.9 + 157.9), and albumin (3.2 + 0.6) indicated an inflammatory state in diverse individuals with lung cancer, with significantly higher NLR (8.5 + 9.7 versus 4.7 + 4.2, p&amp;lt;0.001) and PLR (268.9 + 204.5 versus 198.7 + 108.9, p&amp;lt;0.01) and significantly lower albumin (3.1 + 0.7 versus 3.4 + 0.5, p&amp;lt;0.01) in those with sarcopenia compared to those without sarcopenia. The odds of sarcopenia were 2.2 higher with NLR &amp;gt; 3 compared to NLR &amp;lt;3 (95% CI: 1.1, 4.4) and 2.5 higher with albumin &amp;lt;3.5 compared to albumin &amp;gt;3.5 (95% CI: 1.2, 5.3) after controlling for race/ethnicity, stage of cancer, age, and BMI. PLR &amp;gt; 150 was not a significant predictor of sarcopenia. Conclusion: Diverse individuals with sarcopenia of lung cancer present with higher inflammation compared to individuals with lung cancer but without sarcopenia as indicated by NLR, PLR, and albumin levels. Moderate to high levels of inflammation as indicated by high NLR and low albumin may help predict sarcopenia status in diverse individuals with lung cancer. Citation Format: Cecily A. Byrne, Giamila Fantuzzi, Vanessa M. Oddo, Sage Kim, Timothy J. Koh, Sandra L. Gomez. Inflammatory biomarkers by sarcopenia status in diverse individuals with lung 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 7649.

Abstract 6139: Genetic modifiers of KRAS-mutant colorectal cancer

Abstract Somatic driver mutations in KRAS are found in ~40% of colorectal cancers (CRCs) and are associated with worse outcomes. In the US, individuals of African ancestry with CRC are more likely to have tumors with KRAS mutations than individuals of European ancestry, even after considering differences in socioeconomic status and other risk factors. Germline variants can influence somatic mutation events and may provide a selective advantage such that a mutated cell is more likely to progress to a cancer. Germline variants have been found to associate with somatic mutations in a variety of tumors. Based on ancestry differences in KRAS tumor mutation frequency, we hypothesized that germline variants altering molecular pathways that support KRAS tumorigenesis will associate with KRAS-mutant status. To test this, we performed a two-step association study using KRAS mutation status as our phenotype in individuals with microsatellite stable CRC. First, we conducted a discovery analysis using genome-wide germline genotypes and somatic mutation data from 6,386 non-Hispanic White CRC patients from the Cancer Genome Atlas and the GECCO consortium, considering sex and tumor location as covariates. To select variants for additional study, we used in-silico tools, such as expression quantitative trait loci (eQTL), to predict how associated variants may alter gene expression and chromatin. After reviewing relevant genomic features, excluding SNVs with minor allele frequency &amp;lt;10% and pruning SNVs in linkage disequilibrium (r2&amp;gt;0.75), we identified candidate loci for a multi-ancestry independent validation analysis. In the discovery analysis, no variants met genome-wide significance thresholds (p-value &amp;lt;5x10-8), though 3 SNVs associated with KRAS mutation status with p-values &amp;lt;1x10-6 and 50 with p-values &amp;lt;1x10-5. Of these 50 SNVs, 21 met criteria for validation. We chose 80 additional SNVs (p-value &amp;lt;1x10-4) with predicted functional effect, for a total of 101 SNVs for analyses. In our preliminary validation analysis of 1,487 individuals grouped by self-reported race, no variants had a significant association in all populations. The rs726800 variant showed nominal association with KRAS mutation status (p-value=0.028) in self-reported non-Hispanic White individuals. This variant is within potential cis-regulatory distance of HS3ST3A1 and COX10-DT, both of which have been reported as cancer biomarkers. Nominal associations were identified in self-reported Black (n=7 SNVs) and Hispanic or Latino (n=3 SNVs) individuals, though both groups had limited sample sizes. Additional validation samples are being analyzed, as well as analysis with adjustment for genetic ancestry. Future functional studies of top candidate variants will add mechanistic insight. In summary, we identified germline SNVs that associate with KRAS somatic mutations in CRC and may inform the cellular context that supports development of colorectal tumors with KRAS mutations. Citation Format: Nijole P. Tjader, Johnny Ramroop, Tanish Gandhi, Peter T. Campbell, Andrew T. Chan, Steven Gallinger, Graham G. Giles, Marc J. Gunter, Tabitha A. Harrison, Michael Hoffmeister, Polly A. Newcomb, Shuji Ogino, Amanda I. Phipps, Conghui Qu, Robert E. Schoen, Andrew Pellatt, Michael O. Woods, Bethany Van Guelpen, Patrick Stevens, Heather Hampel, Ulrike Peters, Joseph P. McElroy, Amanda E. Toland. Genetic modifiers of KRAS-mutant colorectal 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 6139.

Metformin’s role in lowering colorectal cancer risk among individuals with diabetes from the Southern Community Cohort Study

BackgroundMetformin, utilized to manage hyperglycemia, has been linked to a reduced risk of colorectal cancer (CRC) among individuals with diabetes. However, evidence is lacking for non-Hispanic Black individuals and those with lower socioeconomic status (SES), who face elevated risk for both diabetes and CRC. In this study, we investigated the association between metformin use and incident CRC risk within the Southern Community Cohort Study (SCCS), a racially- and SES-diverse prospective cohort. MethodsParticipants reported their diabetes diagnosis and medications, including metformin, upon enrollment (2002–2009) and during follow-up surveys approximately every five years. Incident cases of CRC were identified through state cancer registries and the National Death Index. Proportional hazards models were employed to explore the relationship between metformin use and CRC risk, adjusted for cancer risk factors. ResultsA total of 25,992 participants with diabetes were included in the analysis, among whom 10,095 were taking metformin. Of these participants, 76% identified as non-Hispanic Black, and 60% reported household incomes <$15,000/year. Metformin use was associated with a significantly lower CRC risk (HR [95% CI]: 0.71 [0.55–0.93]), with consistent results for both colon (0.80 [0.59–1.07]) and rectal cancers (0.49 [0.28–0.86]). The protective association appeared to be stronger among non-Hispanic White individuals (0.51 [0.31–0.85]) compared to non-Hispanic Black participants (0.80 [0.59–1.08], p-interaction =.13). Additionally, a protective association was observed among obese individuals (BMI ≥30 kg/m2, 0.59 [0.43–0.82] but not among non-obese participants (0.99 [0.65–1.51], p-interaction =.05) ConclusionOur findings indicate that metformin use is associated with a reduced risk of CRC in individuals with diabetes, including among those from predominantly low SES backgrounds. These results support previous epidemiological findings, and demonstrate that the protective association for metformin in relation to incident CRC likely generalizes to populations with higher underlying risk.

Racial and Ethnic Concordance Between National Health Service Corps Clinicians and Underserved Populations

Despite the widely recognized importance of racial and ethnic concordance between patients and clinicians, there is a lack of studies on clinician diversity in medically underserved areas and whether it aligns with the changing demographic landscape. To assess trends in National Health Services Corps (NHSC) clinician diversity and racial and ethnic concordance between NHSC clinicians and the populations in underserved areas from before to after the 2009 NHSC expansion. This cross-sectional, population-based study compared trends in the diversity of NHSC clinicians practicing in health professional shortage areas (HPSAs) and the HPSA populations during 2003 to 2019 using the Health Resources and Services Administration's NHSC Field Strength Database and Area Health Resources Files. The analysis was performed from February through May 2023. Concordance was measured with an annual community representativeness ratio defined as the ratio of the proportions of same race or ethnicity NHSC clinicians to HPSA population. There were a total of 41 180 clinicians practicing in HPSAs from 2003 to 2019; the median (IQR) age was 34 (30-41) years. Among 38 569 NHSC clinicians who reported gender, 28 444 (73.7%) identified as female and 10 125 (26.3%) identified as male. The average annual number of NHSC clinicians increased from 3357 in 2003 to 2008 to 9592 in 2009 to 2019. Before 2009, 1076 clinicians (5.3%) identified as Black, 9780 (48.6%) as Hispanic, 908 (4.5%) as other, and 8380 (41.6%) as White. During this period, concordance was low among non-Hispanic White and Black individuals due to clinician underrepresentation relative to the population, yet Hispanic clinicians were overrepresented. Following the 2009 NHSC expansion, the main change was the sharp decline in the proportion of Hispanic clinicians, to 1601 (13%) by 2019; while concordance was achieved for non-Hispanic White and Black individuals, Hispanic clinicians became underrepresented relative to population. The results held across 3 specialties: primary care, mental health care, and dental care. This cross-sectional study of trends in racial and ethnic concordance found that while the NHSC expansion starting in 2009 improved clinician-population concordance for non-Hispanic White and Black individuals, it reversed a prior trend for Hispanic individuals among whom clinicians became underrepresented relative to the population. Targeted NHSC clinician recruitment efforts are needed to improve concordance for Hispanic individuals in underserved areas, especially given Hispanics' projected growth in the US.

Obesity Disparities Among Adult Single-Race and Multiracial Asian and Pacific Islander Populations

Despite increasing numbers of multiracial individuals, they are often excluded in studies or aggregated within larger race and ethnicity groups due to small sample sizes. To examine disparities in the prevalence of obesity among single-race and multiracial Asian and Pacific Islander individuals compared with non-Hispanic White (hereafter, White) individuals. This cross-sectional study used electronic health record (EHR) data linked to social determinants of health and health behavior data for adult (age ≥18 years) members of 2 large health care systems in California and Hawai'i who had at least 1 ambulatory visit to a primary care practitioner between January 1, 2006, and December 31, 2018. Data were analyzed from October 31, 2022, to July 31, 2023. Self-identified race and ethnicity provided in the EHR as a single-race category (Asian Indian, Chinese, Filipino, Japanese, Native Hawaiian only, Other Pacific Islander, or White) or a multiracial category (Asian and Pacific Islander; Asian, Pacific Islander, and White; Asian and White; or Pacific Islander and White). The main outcome was obesity (body mass index [BMI] ≥30.0), based on last measured height and weight from the EHR. Logistic regression was used to examine the association between race and ethnicity and odds of obesity. A total of 5229 individuals (3055 [58.4%] male; mean [SD] age, 70.73 [11.51] years) were examined, of whom 444 (8.5%) were Asian Indian; 1091 (20.9%), Chinese; 483 (9.2%), Filipino; 666 (12.7%), Japanese; 91 (1.7%), Native Hawaiian; 95 (1.8%), Other Pacific Islander; and 888 (17.0%), White. The percentages of individuals who identified as multiracial were as follows: 417 (8.0%) were Asian and Pacific Islander; 392 (7.5%), Asian, Pacific Islander, and White; 248 (4.7%), Asian and White; and 414 (7.9%), Pacific Islander and White. A total of 1333 participants (25.5%) were classified as having obesity based on standard BMI criteria. Obesity was highest among people who identified as Asian, Pacific Islander, and White (204 of 392 [52.0%]) followed by those who identified as Other Pacific Islander (47 of 95 [49.5%]), Native Hawaiian (44 of 91 [48.4%]), and Pacific Islander and White (186 of 414 [44.9%]). After accounting for demographic, socioeconomic, and health behavior factors, people who identified as Asian, Pacific Islander, and White (odds ratio [OR], 1.80; 95% CI, 1.37-2.38) or Pacific Islander and White (OR, 1.55; 95% CI, 1.18-2.04) had increased odds of obesity compared with White individuals. All single-race Asian groups had lower odds of obesity compared with White individuals: Asian Indian (OR, 0.29; 95% CI, 0.20-0.40), Chinese (OR, 0.22; 95% CI, 0.17-0.29), Filipino (OR, 0.46; 95% CI, 0.35-0.62), and Japanese (OR, 0.38, 95% CI, 0.29-0.50). In this study, multiracial Asian and Pacific Islander individuals had an increased prevalence of obesity compared with many of their single-race counterparts. As the number of multiracial individuals increases, it will be important for clinical and public health systems to track disparities in these populations.

Abstract P361: Health Behaviors, Healthcare Utilization and Social Determinants of Health Among Afro-Latin and Non-Hispanic Black Men at Risk for Hypertension: The CLIP Study

Background: Non-Hispanic Black (NHB) men experience cardiovascular disparities, including high prevalence of hypertension and high morbidity and mortality due to cardiovascular disease (CVD). Less is known about CVD risk among Afro-Latin (AL) men, who are an understudied population overall. The Hispanic/Latin population is the largest and fastest growing ethnic minority group in the United States, as well as one of the most heterogeneous. However, CVD in this population is often examined in aggregate, or by country of origin, and is most often compared to Non-Hispanic White individuals, not only limiting understanding of CVD risk but also potential avenues for intervention. Objective: To describe CVD risk, healthcare utilization and social determinants of health among a sample of AL and NHB men. Methods and Results: We present preliminary data from the Community-to-Clinic Linkage Program (CLIP) study, a community-based cluster randomized trial testing barbershop facilitation to prevent hypertension in normotensive Black men. The study is set in Staten Island (SI), New York City. Approximately 10% of SI residents identify as Black, of which ~ 90% live in 6 zip codes with the highest prevalence of hypertension in the borough. Within the cohort (N=243), AL men (N=88) and NHB men (N=155) had similar blood pressure, but AL men were younger and had lower BMI compared to NHB men, age mean (SD), 35.1 (11.8) years versus 39.2 (12.1) years, p=0.007, BMI 25.6 (4.2) versus 27.2 (5.2) BMI, p=0.01. While diet was similar, AL men had higher levels of weekly physical activity, 5662 (4927) minutes versus 3461 (2453) minutes among NHB men, p&lt;0.001. Both groups had a similar rate of smoking tobacco and there were no differences related to sleep quality or sleep duration. AL men were more likely to have seen a healthcare provider in the last 5 years compared to NHB men and used the emergency room for care more than NHB men, 70.5% versus 47.6%, p=0.02, and 20.4% versus 9.2%, p=0.02, respectively. More AL men delayed medical care because of costs in the last year than NHB men, 8.2% versus 2.3%, p=0.03. Fewer AL men reported having a primary care provider, 19.4% versus 29.3%, p=0.03 compared to NHB men. Both groups reported similar rates of depressive symptoms and social support, but NHB men had higher perceives stress (PSS-4 scores), 6.0 (2.9) versus 4.4 (3.4), p&lt;0.001 than AL men. More AL men were born abroad, 69.4% versus 96.6%, p&lt;0.001 than NHB men. Education attainment was similar between both groups; AL men were more likely to be employed full-time than NHB men, 57.1% versus 51.7%, p=0.04. Income data was limited as approximately a third of men declined to respond. Conclusion: Understanding CVD risk and patterns of healthcare utilization among Afro-Latin and Non-Hispanic Black men will help inform strategies for intervention to improve cardiovascular health and reduce CVD disparities.

Toward a cross-cultural understanding of intraindividual variability metrics

ABSTRACT Objective Compare the construct validity and predictive utility of cognitive intraindividual variability (IIV) in a sample of community-dwelling Hispanic and non-Hispanic white (NHW) older adults. Methods The present study included annual data from 651 older adult control participants (Hispanic = 293; NHW = 358) enrolled in the Texas Alzheimer’s Research and Care Consortium for at least 5 years. Mean composite z-scores were calculated for attention, language, memory, and executive domains. IIV was calculated as was the standard deviation both within (IIV-Within) and between (IIV-Between) these domains. Results At baseline, NHW individuals obtained significantly higher mean scores in each domain than their Hispanic counterparts. They also showed significantly greater variability within and between domains, except for IIV-Within the language domain which was significantly larger in the Hispanic group. IIV-Between domains was driven primarily by IIV-Within the executive function domain in the NHW cohort and by IIV-Within the language domain in the Hispanic cohort. In both groups, the addition of IIV-Within and IIV-Between cognitive domains at baseline significantly improved prediction of global cognitive status after 5 years above and beyond demographic characteristics, genetic and cardiovascular risk. However, IIV-Between domains was the strongest predictor in the NHW group, while IIV-Within the attention domain was the strongest predictor in the Hispanic group. Conclusions Findings suggest that, while IIV-Between domains is a promising adjunctive method for predicting future cognitive decline, its construct validity and predictive utility varies based on ethnic group.

Influence of biopsychosocial factors on self-reported anxiety/depression symptoms among first-generation immigrant population in the U.S.

Despite increasing studies on mental health among immigrants, there are limited studies using nationally representative samples to examine immigrants' mental health and its potential biopsychosocial contributing factors, especially during the COVID-19 pandemic. We explored and estimated the influence of life satisfaction, social/emotional support, and other biopsychosocial factors on self-reported anxiety/depression symptoms among a nationally representative sample of first-generation immigrants in the U.S. We conducted a secondary data analysis using the 2021 National Health Interview Survey among first-generation adults aged ≥ 18 years (n = 4295). We applied survey weights and developed multivariable logistic regression model to evaluate the study objective. The prevalence of daily, weekly, or monthly anxiety/depression symptoms was 10.22% in the first-generation immigrant population. There were 2.04% daily, 3.27% weekly, and 4.91% monthly anxiety/depression among the population: about 8.20%, 9.94%, and 9.60% experienced anxiety symptoms, whereas 2.49%, 3.54%, and 5.34% experienced depression symptoms daily, weekly, and monthly, respectively. The first-generation population aged 26-49 years were less likely to experience anxiety/depression daily, weekly, or monthly compared to those aged 18-25. Females (versus males) were more likely to experience anxiety/depression daily, weekly, or monthly. Those who identified as gay/lesbian had higher odds of experiencing anxiety/depression daily, weekly, or monthly compared to heterosexual persons. Relative to non-Hispanic White individuals, non-Hispanic Asian, Black/African American, and Hispanic individuals had lower odds, while other/multi-racial/ethnic groups were more likely to experience anxiety/depression daily, weekly, or monthly. A higher life satisfaction score was associated with lower odds of experiencing anxiety/depression daily, weekly, or monthly. Having social/emotional support sometimes/rarely or using healthcare within the past one/two years was associated with experiencing anxiety/depression daily, weekly, or monthly. The findings reveal significant burden of anxiety and depression among first-generation population in the U.S., with higher risks among subgroups like young adults, females, sexual minorities, and non-Hispanic White and other/multi-racial individuals. Additionally, individuals with lower life satisfaction scores, limited social/emotional support, or healthcare utilization in the past one or two years present increased risk. These findings highlight the need for personalized mental health screening and interventions for first-generation individuals in the U.S. based on their diversity and health-related risks.

Factors Associated With Long COVID: Insights From Two Nationwide Surveys

BackgroundLong COVID is a multisystemic condition that affects the lives of millions of people globally, yet factors associated with it are poorly defined. Our purpose in this study was to identify factors associated with long COVID. MethodsThis cross-sectional study used data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS) and the 2022 National Health Interview Survey (NHIS). We restricted the sample to individuals aged 18 and older who reported a positive COVID-19 test or doctor's diagnosis. Individuals who reported symptoms of at least 3 months were assumed to have long COVID. We identified demographic and clinical characteristics associated with long COVID, in unadjusted and adjusted analyses. ResultsThe study included 124,313 individuals in the BRFSS cohort and 10,131 in the NHIS cohort who reported a COVID-19 infection, with 26,783 (21.5%) and 1797 (17.7%) reporting long COVID, respectively. We found middle age, female sex, lack of a college degree, and severity of acute COVID-19 infection to be associated with long COVID. In contrast, non-Hispanic Asian and Black Americans were less likely to report long COVID compared with non-Hispanic White individuals. These findings were consistent across datasets. ConclusionsSeveral demographic features were associated with long COVID, which may be the result of social, clinical, or biological influences.

Prevalence, trends, and characteristics of metabolic dysfunction-associated steatotic liver disease among the US population aged 12-79 years.

Clinical observation revealed an increase in metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence among adults and adolescents and young adults (AYA). However, its prevalence trend in specific subgroups and its characteristics are unclear. This cross-sectional study included adults and AYA aged 20-79 and 12-19 years, respectively, from the National Health and Nutrition Examination Survey from 1999 to 2018. MASLD was defined as US Fatty Liver Index ≥30 in adults and alanine amino transaminase elevation and obesity in AYA. Joinpoint and logistic regression were used to evaluate the MASLD prevalence trend and its associated characteristics. MASLD was diagnosed in 17 156 892 of 51 109 914 (33.6%) adults and 1 705 586 of 29 278 666 AYA (5.8%). During the study period, MASLD prevalence significantly increased from 30.8% to 37.7% ( P < 0.01) in adults and in subgroups of female participants, individuals aged 20-45 and 61-79 years, and non-Hispanic white individuals. Conversely, MASLD prevalence did not significantly change in AYA (from 5.1% to 5.2%, P = 0.139), except in the subgroup of Mexican Americans (from 8.2% to 10.8%, P = 0.01). Among adults, high MASLD prevalence was associated with male sex, Mexican American ethnicity, age >50 years, being unmarried, poverty income ratio <130, poor or fair health condition, obesity or overweight, and chronic conditions. Among AYA, high MASLD prevalence was associated with male sex, poverty income ratio <130, and education. Accordingly, we concluded that health care providers should prevent and treat conditions associated with MASLD by raising awareness of the increasing trend of MASLD.