Implementation of Universal Hepatitis C Virus Screening in a Tertiary Cancer Center.

BACKGROUND: The prevalence of chronic hepatitis C virus (HCV) infection in the United States is ≤1%. Universal HCV screening is recommended nationwide. Here we describe our experience implementing universal HCV screening at a cancer center. METHODS: In October 2016, universal HCV screening with HCV antibody (anti-HCV) was initiated for all new outpatients. Universal screening was promoted through widespread provider education, orders in the Epic electronic health records (EHRs), SmartSets, and automated EHR reminders. The effort focused on patients with solid tumors, because universal screening in patients with hematologic malignancies was already standard practice. Primary outcomes were the proportion of patients screened and the proportion of patients with reactive anti-HCV test results linked to HCV care. The secondary outcome was the incidence of HCV-associated hepatocellular carcinoma as a second primary malignancy (HCC-SPM) in patients with a history of other cancers before HCC diagnosis. Epic's Reporting Workbench Business Intelligence tools were used. Statistical significance was defined as P<.05 on chi-square analysis. RESULTS: From April 2016 through April 2023, 56,075 patients with solid tumors were screened for HCV, of whom 1,300 (2.3%) had reactive anti-HCV test results. The proportion of patients screened was 10.1% in the 6 months before study implementation and 34.4% in the last 6 months of the study (P<.001). HCV screening was ordered using SmartSets in 39,332 (45.8%) patients and in response to automated EHR reminders in 10,972 (12.8%) patients. Most patients with reactive anti-HCV test results were linked to care (765/1,300; 59%), most with proven HCV infection were treated (425/562; 76%), and most treated patients achieved sustained virologic response (414/425; 97%). The incidence of HCC-SPMs was 15% in historical controls treated from 2011 to 2017 and 5.7% following implementation of universal screening (P=.0002). CONCLUSIONS: Universal HCV screening can be successfully implemented in cancer hospitals using an EHR-based multipronged approach to eliminate HCV and prevent HCV-associated HCC-SPMs.

Institution-Wide Retreats Foster Organizational Learning and Action at a Comprehensive Cancer Center.

Providing safe and informed healthcare for sexual and gender minority (SGM) individuals with cancer is stymied by the lack of sexual orientation and gender identity (SOGI) data reliably available in health records and by insufficient training for staff. Approaches that support institutional learning, especially around sensitive topics, are essential for hospitals seeking to improve practices impacting patient safety and research. We engineered annual institutional retreats to identify and unify stakeholders, promote awareness of gaps and needs, identify initiatives, minimize redundant projects, and coordinate efforts that promote improvements in SGM cancer care, education, and research. The 2022 and 2023 retreats employed a 4-h hybrid format allowing virtual and in-person engagement. Retreat organizers facilitated small-group discussions for brainstorming among participants. We performed descriptive statistics from retreat evaluations. The retreats engaged 104 attendees from distinct departments and roles. Participants expressed robust satisfaction, commending the retreat organization and content quality. Notably, the first retreat yielded leadership endorsement and funding for a Quality Improvement pilot to standardize SOGI data collection and clinical staff training. The second retreat provided a platform for updates on focused efforts across the institution and for receiving direction regarding national best practices for SGM care and research. We report the processes and outcomes of institution-wide retreats, which served as a platform for identifying gaps in organizational healthcare practices and research for SGM individuals with cancer. The strategies described herein may be readily scaled at other cancer hospitals seeking to learn and enact system-wide practice changes that support the needs of SGM patients and families.

Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Reducing risk for chronic disease: evaluation of a collective community approach to sustainable evidence-based health programming.

BACKGROUND: Community initiatives can shape health behaviors, such as physical activity and dietary habits, across a population and help reduce the risk of developing chronic disease. To achieve this goal and impact health outcomes, Pasadena Vibrant Community aimed to engage communities in an ongoing dialogue about the importance of healthy behaviors, implement and advance community-based strategies to promote health, and improve diet and physical activity behaviors. The initiative was centered around a collaboration between a backbone organization, steering committee, and 7 collaborating organizations funded to implement multicomponent, evidence-based programs.. The common agenda was detailed in a community action plan, which included 19 interventions targeting healthy eating and active living among adults and youth in Pasadena, Texas. METHODS: A mixed methods evaluation of the initiative was conducted over 4 years. Data sources included document reviews of quarterly progress reports (n = 86) and supplemental data reports (n = 16) provided by collaborating organizations, annual Steering Committee surveys (n = 4), and interviews conducted with staff from a subset of Collaborating Organizations (n = 4). RESULTS: The initiative reached over 50,000 community members per year through 19 evidence-based interventions and impacted health outcomes, including knowledge and adoption of healthy eating practices and increased physical activity. Thirty-one systems-level changes were implemented during the initiative, including 16 environmental changes. Steering Committee meetings and shared goals enabled connections, communication, and cooperation, which allowed Collaborating Organizations to address challenges and combine resources to deliver their programs. CONCLUSIONS: Community initiatives can effectively permeate the community by reaching individuals, improving physical activity and dietary habits, and ensuring sustainability. Based on the experience reported here, the success of a community initiative can be facilitated if collaborating organizations come together to implement evidence-based interventions and tailor them to the community, and if they are empowered by significant leadership and supportive collaboration and aligned by a common agenda.

Recent American College of Physicians Guidance Statement for Screening Average-risk, Asymptomatic Adults for Colorectal Cancer.

The American College of Physicians (ACP) update of their standing guidance statement for colorectal-cancer screening in asymptomatic average-risk adults was recently published to assist clinicians with implementing evidence-based patient care. After assessing existing guideline literature, the ACP recommended five actions: consider not screening adults ages 45 to 49 years; stop screening adults older than 75 years; discuss benefits, harms, costs, availability, frequency, and patient values/preferences with patients prior to choosing a screening method; and when choosing, recommend biennial rather than annual use of a fecal immunochemical test or a guaiac fecal occult blood test and avoid recommending computed tomography colonography or stool DNA tests. While the ACP guidelines are rigorous, well-intended, and considerate of patients' input, their greatest impact may result from highlighting the need for researchers to help frontline clinicians to describe the risk, costs, and benefits/harms of various colorectal-cancer screening strategies in an effective, yet time-efficient, manner given the all-too-brief annual patient encounters. In the United States, reimbursement is still dependent on U.S. Preventive Services Task Force recommendations which are somewhat more liberal in contrast to the ACP's approach which strongly favors randomized, controlled trial evidence to guide the delivery of prevention and screening services to asymptomatic average-risk patients.

Be Well™ Acres Homes: a community-driven, evidence-based approach to reduce health inequities through sustained cross-sector partnership.

PURPOSE: Be Well Communities™ is MD Anderson's signature place-based approach for cancer prevention and control, working with communities to promote wellness and address modifiable risk factors for cancer. The purpose of this paper is to describe implementation of the planning phase of the Be Well Communities model in Acres Homes which began in 2019. METHODS: A community advisory group (Steering Committee) including residents, non-profit organizations, health care partners, city and county agencies, plus other stakeholders, was convened and aligned through a structured process to develop shared goals, foster multisector collaboration, as measured by a stakeholder survey administered twice, and enhance community capacity to improve health outcomes through development of a Community Action Plan. RESULTS: Clear, achievable goals were developed, multisector collaboration was enhanced, and more than 400 h of capacity building support led to a Community Action Plan initially focused on healthy eating and active living, including 15 evidence-based interventions led by 18 organizations. The majority (93%) of the Steering Committee reports that this plan reflects community priorities and will reach the residents most in need. CONCLUSION: By listening and developing trust, the Be Well Communities team successfully worked with Acres Homes residents and organizations to enhance community capacity to address health inequities in one of Houston's most diverse and historic communities.

Addressing cervical cancer disparities in Texas: Expansion of a community-based prevention initiative for medically underserved populations.

Although cervical cancer is preventable, significant disparities exist in access to screening and prevention services. In medically underserved areas (MUAs) of Texas, these rates are 55% higher compared to the remainder of the US. In 2019, we expanded a multicomponent, comprehensive program to improve cervical cancer prevention in partnership with 13 clinics and mobile vans in MUAs of Texas. Our multicomponent intervention program consists of community education and patient navigation coupled with a training/mentoring program for local medical providers to perform diagnostic procedures and treatment for patients with abnormal screening results. Hands-on training courses to learn these skills are coupled with biweekly telementoring conferences using Project ECHO® (Extension for Community Healthcare Outcomes). This program was implemented in 2015 and expanded to other MUAs in Texas in 2019. From March 2019 to August 2022, 75,842 individuals were educated about cervical cancer screening and HPV vaccination. A total of 44,781 women underwent screening for cervical cancer, and 2,216 underwent colposcopy and 264 underwent LEEP. High-grade cervical dysplasia was diagnosed in 658 individuals and invasive cervical cancer in 33 individuals. We trained 22 providers to perform colposcopy and/or LEEP. In addition, 78 Project ECHO telementoring sessions were held with an average of 42 attendees per session, with 72 individual patient cases discussed. Our comprehensive community-based prevention initiative for medically underserved populations has led to a significant number of individuals undergoing cervical cancer screening in MUAs, as well as improved access to colposcopy and LEEP services.

Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.

Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma.

BACKGROUND: It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States. METHODS: We conducted a case-control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor. RESULTS: Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P < 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively. CONCLUSIONS: In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals. IMPACT: The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.

From Premalignant Biology to Precision Interception: Connecting the Dots with a Curated Collection of Invited Articles.

Nearly all cancers have identifiable histologically defined precursors known as precancers. These precancers offer a window of opportunity to intercept the neoplastic process to prevent its development into invasive cancer. However, lack of knowledge regarding the evolution of precancers and the microenvironmental pressures shaping them precludes efforts to intercept them. Technological developments over the past decade have facilitated the study of precancers at a previously unattainable resolution. Calls for a national PreCancer Atlas effort incorporating these technologies were heeded in 2018, with the launch of the Human Tumor Atlas Network (HTAN) as part of the Beau Biden National Cancer Moonshot. Since then, five funded HTAN groups have focused their efforts on profiling precancers from breast, colon, skin, and lung. In this time, what progress has been made? What is next for HTAN and the field of premalignant biology? And are there lessons that individual investigators and the larger prevention field can learn from this initial effort to accelerate the development of novel early detection methods, risk prediction biomarkers, and interception agents? A special collection of invited reviews by experts in cancer evolution, systems biology, immunology, cancer genetics, preventive agent development, among other areas, attempts to answer these questions.

Creating and Activating an Implementation Community to Drive HPV Vaccine Uptake in Texas: The Role of an NCI-Designated Cancer Center.

The University of Texas MD Anderson Cancer Center, a comprehensive cancer center designated by the National Cancer Institute (NCI), defines its service population area as the State of Texas (29.1 M), the second most populous state in the country and the state with the greatest number of uninsured residents in the United States. Consistent with a novel and formal commitment to prevention as part of its core mission, alongside clear opportunities in Texas to drive vaccine uptake, MD Anderson assembled a transdisciplinary team to develop an institutional Framework to increase adolescent HPV vaccination and reduce HPV-related cancer burden. The Framework was developed and activated through a four-phase approach aligned with the NCI Cancer Center Support Grant Community Outreach and Engagement component. MD Anderson identified collaborators through data-driven outreach and constructed a portfolio of collaborative multi-sector initiatives through review processes designed to assess readiness, impact and sustainability. The result is an implementation community of 78 institutions collaboratively implementing 12 initiatives within a shared measurement framework impacting 18 counties. This paper describes a structured and rigorous process to set up the implementation of a multi-year investment in evidence-based strategies to increase HPV vaccination that solves challenges preventing implementation of recommended strategies and to encourage similar initiative replication.

Ten Years of the International Cancer Control Partnership: Promoting National Cancer Control Plans to Shape the Health System Response for Cancer Control.

Growing premature mortality because of cancer is an increasing public health concern in all countries. This article reviews 10 years of the International Cancer Control Partnership (ICCP) considering the themes of National Cancer Control Plan (NCCP) support, technical assistance, governance, and the renewed momentum of global calls to action. ICCP has provided key resources for the cancer community by hosting a portal with national cancer control and noncommunicable disease (NCD) plans, strategies, guidelines, and key implementation guides for a growing community of best practices. ICCP partners have responded to the changing needs of country planners, adjusting technical guidance as needs evolve from planning to implementation at the national level with an associated shift to peer-to-peer learning and knowledge exchange. The ICCP offer to assist countries in cancer planning continues to be relevant as countries focus on implementation of global initiatives for breast, cervical, and childhood cancers. These initiatives are important to drive priority actions and a systems approach in the emerging road map on NCDs-a message that will be supported by a second global review of NCCPs in 2023. This is critical for driving national action in all countries on cancer and other NCDs in line with global health commitments made for 2030 and adopted by the United Nations General Assemblies. ICCP sees robust systems and financial planning for implementation, monitoring, and evaluation of NCCPs and protection from cancer-related catastrophic expenditure, as critical to longer-term sustainability and success. ICCP calls for national policymakers to prioritize integration of cancer prevention and control into emerging universal health care approaches, including pandemic preparedness/health system resilience and calls for an equity focus in new NCCPs.

A Comprehensive Program to Reduce Tobacco-related Cancers Through Actions by a National Cancer Institute-designated Cancer Center.

Tobacco use accounts for 30% of all cancer-related deaths worldwide and 20% in the US, despite effective, evidence-based interventions for reducing tobacco use and tobacco-related cancers and deaths. In 2012, to reduce the burden of tobacco-related cancer and associated population-level risks across Texas, The University of Texas MD Anderson Cancer Center initiated the EndTobacco® program to promote statewide cancer control activities. We created evidence-based initiatives, established selection criteria, and implemented actions involving policy, education, and tobacco treatment services. As a result, EndTobacco has supported, educated, and convened local and state coalitions in policymaking; provided tobacco treatment education to health professionals; implemented Texas' only certified tobacco treatment training program; and led an initiative to enhance the tobacco-free culture of the state's publicly funded university system. Supported by commitments from MD Anderson, we developed and implemented evidence-based actions for tobacco control tailored to the center's mission, values, expertise, resources, and partnerships. By 2021, the adult smoking rate in Texas dropped from 19.2% (2014) to 13.2%. Contributors to this drop include state tobacco control policies, programs and services from multiple agencies and associations, and EndTobacco activities that complement the statewide effort to prevent youth smoking initiation and increase quit attempts among youth and adults.

Development, Implementation, and Evaluation of a Distance Learning and Telementoring Program for Cervical Cancer Prevention in Cameroon.

Importance: Although Africa has the highest burden of cervical cancer in the world, educational resources to achieve the 90-70-90 targets set by the World Health Organization in its strategy to eliminate cervical cancer are lacking in the region. Objectives: To adapt, implement, and evaluate the Project Extension for Community Health Care Outcomes (ECHO), an innovative learning tool, to build capacity of clinicians to better incorporate new evidence-based guidelines into cervical cancer control policies and clinical practices. Design, Setting, and Participants: This cross-sectional study assessed knowledge and practices of clinicians and support staff regarding cervical cancer prevention and control and compared them among respondents who had attended Project ECHO sessions (prior ECHO attendees) with those who had not but were planning on attending in the near future (newcomers) as part of the Cameroon Cervical Cancer Prevention Project ECHO. Satisfaction of prior ECHO attendees was also evaluated. Data were analyzed from January to March 2022. Main Outcomes and Measures: Main outcomes were practices and knowledge regarding cervical cancer education and prevention and preinvasive management procedures compared among prior ECHO attendees and newcomers. Results: Of the 75 participants (mean [SD] age, 36.4 [10.0] years; 65.7% [95% CI, 54.3%-77.1%] women) enrolled in this study, 41 (54.7%; 95% CI, 43.1%-66.2%) were prior ECHO attendees, and most were clinicians (55 respondents [78.6%; 95% CI, 68.7%-88.4%]). Overall, 50% (95% CI, 37.8%-62.2%) of respondents reported performing cervical cancer screening with visual inspection of the cervix after application of acetic acid (VIA) and/or visual inspection of the cervix after application of Lugol's iodine (VILI), 46.3% (95% CI, 34.0%-58.5%) of respondents reported performing human papillomavirus (HPV) testing, and 30.3% (95% CI, 18.9%-41.7%) of respondents reported performing cervical cytological examination in their practices, Approximately one-fourth of respondents reported performing cryotherapy (25.4% [95% CI, 14.7%-36.1%]), thermal ablation (27.3% [95% CI, 16.2%-38.3%]) or loop electrosurgical excisional procedure (LEEP, 25.0% [95% CI, 14.4%-35.6%]) for treatment of preinvasive disease. The clinical use of many of these screening and treatment tools was significantly higher among prior ECHO attendees compared with newcomers (VIA/VILI: 63.2% [95% CI, 47.4%-78.9%] vs 33.3% [95% CI, 16.0%-50.6%]; P = .03; cryotherapy: 40.5% [95% CI, 24.3%-56.8%] vs 6.7% [95% CI, 0.0%-15.8%]; P = .002; thermal ablation: 43.2% [95% CI, 26.9%-59.6%] vs 6.9% [95% CI, 0.0%-16.4%]; P = .002). Knowledge about cervical cancer education, prevention, and management procedures was satisfactory in 36.1% (95% CI, 23.7%-48.5%) of respondents; this proportion was significantly higher among prior ECHO attendees (53.8% [95% CI, 37.7%-69.9%]) compared with newcomers (4.5% [95% CI, 0.0%-13.5%]; P < .001). Approximately two-thirds of participants (68.8% [95% CI, 51.8%-85.8%]) reported that they had applied knowledge learned in our ECHO sessions to patient care in their practice or adopted best-practice care through their participation in this ECHO program. Conclusions and Relevance: These findings suggest that the Project ECHO e-learning and telementoring program was associated with improved skills for clinicians and support staff and enhanced quality of care for patients. In the COVID-19 era and beyond, reinforced efforts to strengthen cervical cancer knowledge and best practices through distance learning and collaboration are needed.

Vulvar Cancer Incidence in the United States and its Relationship to Human Papillomavirus Vaccinations, 2001-2018.

The human papillomavirus (HPV) vaccine was indicated for the prevention of vulvovaginal cancers in 2008, but its impact on the incidence of vulvar cancers within the US is unknown. To determine this, we conducted a secondary analysis of 88,942 vulvar cancer cases among women 20+ years old using the US Cancer Statistics 2001-2018 databases. Data were stratified by tumor behavior (in situ or invasive), age (20-44, 45-64, 65+ years old), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), and US census region (Northeast, South, Midwest, West), and incidence rates and average annual percentage changes (AAPC) were calculated by group. Reversing previous trends, the incidence of vulvar carcinoma in situ significantly decreased between 2001 and 2018 among women from all age groups, races/ethnicities, and regions (combined AAPC,  -4.3; 95% confidence interval (CI), -4.7 to -3.8). The incidence of invasive vulvar squamous cell carcinoma decreased significantly among 20- to 44-year-old women (AAPC, -0.8; 95% CI, -1.3 to -0.3), but significantly increased among those 45 to 64 (AAPC, 2.3; 95% CI, 1.8-2.8) and 65+ years old (AAPC, 1.2; 95% CI, 1.1-1.4). Regardless of tumor behavior, incidence was highest among non-Hispanic Whites and the Midwest region. Overall, the significant declines in vulvar carcinoma in situ among all ages, as well as invasive vulvar cancer among younger women, are encouraging and complement other recent data suggesting HPV vaccinations are already reducing anal and cervical cancer incidence. Over time, further declines in vulvar carcinoma incidence are likely as uptake and completion rates of the HPV vaccine increase in the US. PREVENTION RELEVANCE: We found evidence that HPV vaccinations likely contributed to a decrease in the incidences of vulvar carcinoma in situ and invasive vulvar carcinoma among 20- to 44-year-old women between 2001 and 2018. Our data add to the growing evidence that HPV vaccinations are reducing the incidence of HPV-related anogenital cancers.

Gut Microbiome Alterations Associated with Diabetes in Mexican Americans in South Texas.

Mexican Americans have a high prevalence of diabetes and burden of diabetes-related complications, highlighting the need for novel preventive strategies and noninvasive predictors of diabetes risk tailored to this population. Changes in the gut microbiome have the potential to predict diabetes. Here, we aimed to identify alterations in the gut microbiome associated with diabetes in the high-risk population of Mexican Americans in South Texas. Stool samples were collected from 216 subjects from the population-based Cameron County Hispanic Cohort. Among them, 75 had type 2 diabetes. Taxonomic and functional profiling of the stool samples were assessed by 16S and shotgun metagenomic sequencing, and the influence of genetic factors was explored. The gut microbiome of subjects with diabetes was enriched with proinflammatory Proteobacteria members (Enterobacteriaceae, Escherichia-Shigella) and depleted of butyrate-producing Clostridiales members (Faecalibacterium prausnitzii, Peptostreptococcaceae, and Clostridium sensu stricto 1). The accompanying metagenomic changes in subjects with diabetes suggested dysregulated amino acid metabolism, reduced galacturonate and glucuronate catabolism (correlating with Faecalibacterium prausnitzii abundance), and enriched heme biosynthesis (correlating with Enterobacteriaceae abundance). Polymorphism rs7129790 near MMP27 was strongly associated with high Proteobacteria abundance and was more frequent in this cohort and in individuals of Mexican ancestry than in Europeans. In conclusion, Mexican Americans in South Texas with diabetes display distinct gut microbiome and metagenomic signatures. These signatures may have utility in risk modeling and disease prevention in this high-risk population. IMPORTANCE The gut microbiome composition varies across ethnicities and geographical locations, yet studies on diabetes-associated microbiome changes specific to high-risk Mexican Americans are lacking. Here, we aimed to identify specific alterations associated with diabetes in this population, as well as host genetic factors that may explain increased disease susceptibility in this ethnic group. Using samples from a population-based cohort of Mexican Americans with a high prevalence of obesity and diabetes, we confirmed findings from studies on other ethnicities that suggested promotion of a chronic proinflammatory environment, loss of butyrate production, and compromised intestinal barrier integrity. High abundance of proinflammatory Proteobacteria was associated with a polymorphism that was more frequent in this cohort and in individuals of Mexican ancestry than in Europeans. Validation of microbiome-based risk models for diabetes should be evaluated in prospective cohort studies.

Multicancer early detection test: Preclinical, translational, and clinical evidence-generation plan and provocative questions.

Minimally invasive molecular biomarkers have been applied to the early detection of multiple cancers in large scale case-control and cohort studies. These demonstrations of feasibility herald the potential for permanent transformation of current cancer screening paradigms. This commentary discusses the major opportunities and challenges facing the preclinical development and clinical validation of multicancer early detection test strategies. From a diverse set of early detection research perspectives, the authors recommend specific approaches and highlight important questions for future investigation.

Gut microbiome features associated with liver fibrosis in Hispanics, a population at high risk for fatty liver disease.

BACKGROUND AND AIMS: Hispanics are disproportionately affected by NAFLD, liver fibrosis, cirrhosis, and HCC. Preventive strategies and noninvasive means to identify those in this population at high risk for liver fibrosis, are urgently needed. We aimed to characterize the gut microbiome signatures and related biological functions associated with liver fibrosis in Hispanics and identify environmental and genetic factors affecting them. APPROACH AND RESULTS: Subjects of the population-based Cameron County Hispanic Cohort (CCHC; n = 217) were screened by vibration-controlled transient elastography (FibroScan). Among them, 144 (66.7%) had steatosis and 28 (13.0%) had liver fibrosis. The gut microbiome of subjects with liver fibrosis was enriched with immunogenic commensals (e.g., Prevotella copri, Holdemanella, Clostridiaceae 1) and depleted of Bacteroides caccae, Parabacteroides distasonis, Enterobacter, and Marinifilaceae. The liver fibrosis-associated metagenome was characterized by changes in the urea cycle, L-citrulline biosynthesis and creatinine degradation pathways, and altered synthesis of B vitamins and lipoic acid. These metagenomic changes strongly correlated with the depletion of Parabacteroides distasonis and enrichment of Prevotella and Holdemanella. Liver fibrosis was also associated with depletion of bacterial pathways related to L-fucose biosynthesis. Alcohol consumption, even moderate, was associated with high Prevotella abundance. The single-nucleotide polymorphisms rs3769502 and rs7573751 in the NCK adaptor protein 2 (NCK2) gene positively associated with high Prevotella abundance. CONCLUSION: Hispanics with liver fibrosis display microbiome profiles and associated functional changes that may promote oxidative stress and a proinflammatory environment. These microbiome signatures, together with NCK2 polymorphisms, may have utility in risk modeling and disease prevention in this high-risk population.