Prevalence of the cagA Virulence Factor Varies by Race Among Helicobacter pylori -Infected Patients Undergoing Upper Endoscopy.

Introduction: We designed a race-conscious study to assess the presence of Helicobacter pylori v irulence factor cagA in a retrospective cohort of patients with active H. pylori infection.

Methods: We compared cagA status by race in gastric tissue samples from 473 patients diagnosed with active H.

Helicobacter pylori testing prior to or at gastric cancer diagnosis and survival in a diverse US patient population.

Background: Gastric cancer (GC) accounts for the greatest disparity in cancer mortality between Black and White Americans. Although clinical trials have shown that Helicobacter pylori (Hp) treatment reduces risk of GC, Hp testing and treatment is not consistently performed in the US, and may offer an opportunity to improve survival.

Methods: In a diverse retrospective cohort of 99 GC cases diagnosed at Duke University from 2002-2020 (57% Black; 43% white), we examined the association of Hp testing and treatment prior to or at cancer diagnosis with overall survival using Cox regression analyses to calculate adjusted hazards ratios (HRs) and 95% confidence intervals (CIs).

Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis.

Unlabelled: Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains high, and long-term survival outcomes remain poor. In a search for new therapeutic targets for this disease, we observed that elevated expression of the serine/threonine kinase calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) is highly correlated with tumor invasiveness.

Ca /Calmodulin Dependent Protein Kinase Kinase-2 (CaMKK2) promotes Protein Kinase G (PKG)-dependent actin cytoskeletal assembly to increase tumor metastasis.

Triple-negative breast cancers (TNBCs) tend to become highly invasive early during cancer development. Despite some successes in the initial treatment of patients diagnosed with early-stage localized TNBC, the rate of metastatic recurrence remains high with poor long-term survival outcomes. Here we show that elevated expression of the serine/threonine-kinase, Calcium/Calmodulin (CaM)-dependent protein kinase kinase-2 (CaMKK2), is highly correlated with tumor invasiveness.

Modifiable patient-reported factors associated with cancer-screening knowledge and participation in a community-based health assessment.

Background: We sought to identify modifiable factors associated with cancer screening in a community-based health assessment.

Methods: 24 organizations at 47 community events in central North Carolina distributed a 91-item survey from April-December 2017. Responses about (1) interest in disease prevention, (2) lifestyle choices (e.

Initial Longitudinal Outcomes of Risk-Stratified Men in Their Forties Screened for Prostate Cancer Following Implementation of a Baseline Prostate-Specific Antigen.

Purpose: Prostate cancer (PCa) screening can lead to potential over-diagnosis/over-treatment of indolent cancers. There is a need to optimize practices to better risk-stratify patients. We examined initial longitudinal outcomes of mid-life men with an elevated baseline prostate-specific antigen (PSA) following initiation of a novel screening program within a system-wide network.

A widespread length-dependent splicing dysregulation in cancer.

Dysregulation of alternative splicing is a key molecular hallmark of cancer. However, the common features and underlying mechanisms remain unclear. Here, we report an intriguing length-dependent splicing regulation in cancers.

Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk.

Limited efforts have been made in assessing the effect of genome-wide profiling of RNA splicing-related variation on lung cancer risk. In the present study, we first identified RNA splicing-related genetic variants linked to lung cancer in a genome-wide profiling analysis and then conducted a two-stage (discovery and replication) association study in populations of European ancestry. Discovery and validation were conducted sequentially with a total of 29,266 cases and 56,450 controls from both the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium as well as the OncoArray database.

A single-site pilot feasibility randomized trial of a supportive care mobile application intervention for patients with advanced cancer and caregivers.

Purpose: Mobile health interventions can improve patient care. We developed the Digital Supportive Care Awareness and Navigation (D-SCAN) application (app) to facilitate symptom monitoring and use/awareness of cancer supportive care resources. This study tested feasibility, usability/satisfaction, and preliminary efficacy of D-SCAN.

Adaptive stress response genes associated with breast cancer subtypes and survival outcomes reveal race-related differences.

Aggressive breast cancer variants, like triple negative and inflammatory breast cancer, contribute to disparities in survival and clinical outcomes among African American (AA) patients compared to White (W) patients. We previously identified the dominant role of anti-apoptotic protein XIAP in regulating tumor cell adaptive stress response (ASR) that promotes a hyperproliferative, drug resistant phenotype. Using The Cancer Genome Atlas (TCGA), we identified 46-88 ASR genes that are differentially expressed (2-fold-change and adjusted p-value < 0.

Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.

Background: Prostate cancer is a clinically and molecularly heterogeneous disease, with highest incidence and mortality among men of African ancestry. To date, prostate cancer patient-derived xenograft (PCPDX) models to study this disease have been difficult to establish because of limited specimen availability and poor uptake rates in immunodeficient mice. Ancestrally diverse PCPDXs are even more rare, and only six PCPDXs from self-identified African American patients from one institution were recently made available.

A Zebrafish Model of Metastatic Colonization Pinpoints Cellular Mechanisms of Circulating Tumor Cell Extravasation.

Metastasis is a multistep process in which cells must detach, migrate/invade local structures, intravasate, circulate, extravasate, and colonize. A full understanding of the complexity of this process has been limited by the lack of ability to study these steps in isolation with detailed molecular analyses. Leveraging a comparative oncology approach, we injected canine osteosarcoma cells into the circulation of transgenic zebrafish with fluorescent blood vessels in a biologically dynamic metastasis extravasation model.

Dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes hepatobiliary carcinogenesis in non-alcoholic fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD), the hepatic correlate of the metabolic syndrome, is a major risk factor for hepatobiliary cancer (HBC). Although chronic inflammation is thought to be the root cause of all these diseases, the mechanism whereby it promotes HBC in NAFLD remains poorly understood. Herein, we aim to evaluate the hypothesis that inflammation-related dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes HB carcinogenesis.

A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.

Background: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race.

Methods: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC.

An innovative educational program for addressing health disparities in translational cancer research.

North Carolina Central University (NCCU) and Duke Cancer Institute implemented an NCI-funded Translational Cancer Disparities Research Partnership to enhance translational cancer research, increase the pool of underrepresented racial and ethnic group (UREG) researchers in the translational and clinical research workforce, and equip UREG trainees with skills to increase diversity in clinical trials. The Cancer Research Education Program (C-REP) provided training for UREG graduate students and postdoctoral fellows at Duke and NCCU. An innovative component of C-REP is the Translational Immersion Experience (TIE), which enabled Scholars to gain knowledge across eight domains of clinical and translational research (clinical trials operations, data monitoring, regulatory affairs, UREG accrual, biobanking, community engagement, community outreach, and high-throughput drug screening).

Differential alternative RNA splicing and transcription events between tumors from African American and White patients in The Cancer Genome Atlas.

Individuals of African ancestry suffer disproportionally from higher incidence, aggressiveness, and mortality for particular cancers. This disparity likely results from an interplay among differences in multiple determinants of health, including differences in tumor biology. We used The Cancer Genome Atlas (TCGA) SpliceSeq and TCGA aggregate expression datasets and identified differential alternative RNA splicing and transcription events (ARS/T) in cancers between self-identified African American (AA) and White (W) patients.

Biological Aspects of Cancer Health Disparities.

Racial and ethnic disparities span the continuum of cancer care and are driven by a complex interplay among social, psychosocial, lifestyle, environmental, health system, and biological determinants of health. Research is needed to identify these determinants of cancer health disparities and to develop interventions to achieve cancer health equity. Herein, we focus on the overall burden of ancestry-related molecular alterations, the functional significance of the alterations in hallmarks of cancer, and the implications of the alterations for precision oncology and immuno-oncology.

RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry.

Objectives: Despite disparities in lung cancer incidence and mortality, the molecular landscape of lung cancer in patients of African ancestry remains underexplored, and race-related differences in RNA splicing remain unexplored.

Materials And Methods: We identified differentially spliced genes (DSGs) and differentially expressed genes (DEGs) in biobanked lung squamous cell carcinoma (LUSC) between patients of West African and European ancestry, using ancestral genotyping and Affymetrix Clariom D array. DSGs and DEGs were validated independently using the National Cancer Institute Genomic Data Commons.

Changing the landscape of non-small cell lung cancer disparities.

In the United States, lung and bronchus cancers are the second most common types of cancer and are responsible for the largest number of deaths from cancer, with African Americans suffering disproportionately from lung and bronchus cancers. This disparity likely results from a complex interplay among social, psycho-social, lifestyle, environmental, health system, and biological determinants of health. Toward improving outcomes for lung cancer patients of all races and ethnicities and mitigating lung cancer disparities, in this commentary, we bring forward biological factors that contribute to lung cancer disparities, efforts to identify, functionally characterize, and modulate novel ancestry-related RNA splicing-related targets in lung cancer for precision intervention, and translational and clinical research needs to improve outcomes for lung cancer patients of all races and ethnicities and mitigate lung cancer disparities.

Implementation and Impact of a Risk-Stratified Prostate Cancer Screening Algorithm as a Clinical Decision Support Tool in a Primary Care Network.

Background: Implementation methods of risk-stratified cancer screening guidance throughout a health care system remains understudied.

Objective: Conduct a preliminary analysis of the implementation of a risk-stratified prostate cancer screening algorithm in a single health care system.

Design: Comparison of men seen pre-implementation (2/1/2016-2/1/2017) vs.

The Durham Initiative for Stomach Health (DISH): a pilot community-based Helicobacter pylori education and screening study.

Background: Approximately 15% of all cancers are due to infection. The bacteria Helicobacter pylori is the single leading carcinogenic infectious agent and the main cause of stomach cancer. Prevalence of H.

Project PLACE: Enhancing community and academic partnerships to describe and address health disparities.

Achieving cancer health equity is a national imperative. Cancer is the second leading cause of death in the United States and in North Carolina (NC), where the disease disproportionately impacts traditionally underrepresented race and ethnic groups, those who live in rural communities, the impoverished, and medically disenfranchised and/or health-disparate populations at high-risk for cancer. These populations have worse cancer outcomes and are less likely to be participants in clinical research and trials.