RESUMO
A better understanding of COVID-19 in people with primary immunodeficiency (PI), rare inherited defects in the immune system, is important for protecting this population, especially as population-wide approaches to mitigation change. COVID-19 outcomes in the PI population could have broader public health implications because some people with PI might be more likely to have extended illnesses, which could lead to increased transmission and emergence of variants. We performed a systematic review on COVID-19-associated morbidity and mortality in people with PI. Of the 1114 articles identified through the literature search, we included 68 articles in the review after removing 1046 articles because they were duplicates, did not involve COVID-19, did not involve PI, were not in English, were commentaries, were gene association or gene discovery studies, or could not be accessed. The 68 articles included outcomes for 459 people with PI and COVID-19. Using data from these 459 people, we calculated a case fatality rate of 9%, hospitalization rate of 49%, and oxygen supplementation rate of 29%. Studies have indicated that a number of people with PI showed at least some immune response to COVID-19 vaccination, with responses varying by type of PI and other factors, although vaccine effectiveness against hospitalization was lower in the PI population than in the general population. In addition to being up-to-date on vaccinations, current strategies for optimizing protection for people with PI can include pre-exposure prophylaxis for those eligible and use of therapeutics. Overall, people with PI, when infected, tested positive and showed symptoms for similar lengths of time as the general population. However, a number of people with X-linked agammaglobulinemia (XLA) or other B-cell pathway defects were reported to have prolonged infections, measured by time from first positive SARS-CoV-2 test to first negative test. As prolonged infections might increase the likelihood of genetic variants emerging, SARS-CoV2 isolates from people with PI and extended illness would be good candidates to prioritize for whole genome sequencing.
Assuntos
COVID-19 , Vacinas contra COVID-19 , Humanos , Avaliação de Resultados em Cuidados de Saúde , RNA Viral , SARS-CoV-2RESUMO
Recent reviews have emphasized the need for a health equity agenda in genomics research. To ensure that genomic discoveries can lead to improved health outcomes for all segments of the population, a health equity agenda needs to go beyond research studies. Advances in genomics and precision medicine have led to an increasing number of evidence-based applications that can reduce morbidity and mortality for millions of people (tier 1). Studies have shown lower implementation rates for selected diseases with tier 1 applications (familial hypercholesterolemia, Lynch syndrome, hereditary breast and ovarian cancer) among racial and ethnic minority groups, rural communities, uninsured or underinsured people, and those with lower education and income. We make the case that a public health agenda is needed to address disparities in implementation of genomics and precision medicine. Public health actions can be centered on population-specific needs and outcomes assessment, policy and evidence development, and assurance of delivery of effective and ethical interventions. Crucial public health activities also include engaging communities, building coalitions, improving genetic health literacy, and building a diverse workforce. Without concerted public health action, further advances in genomics with potentially broad applications could lead to further widening of health disparities in the next decade.
Assuntos
Equidade em Saúde , Etnicidade , Genômica , Humanos , Grupos Minoritários , Medicina de Precisão , Saúde PúblicaRESUMO
Public health plays an important role in ensuring access to interventions that can prevent disease, including the implementation of evidence-based genomic recommendations. We used the Centers for Disease Control and Prevention (CDC) Science Impact Framework to trace the impact of public health activities and partnerships on the implementation of the 2009 Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Lynch Syndrome screening recommendation and the 2005 and 2013 United States Preventive Services Task Force (USPSTF) BRCA1 and BRCA2 testing recommendations.The EGAPP and USPSTF recommendations have each been cited by >300 peer-reviewed publications. CDC funds selected states to build capacity to integrate these recommendations into public health programs, through education, policy, surveillance, and partnerships. Most state cancer control plans include genomics-related goals, objectives, or strategies. Since the EGAPP recommendation, major public and private payers now provide coverage for Lynch Syndrome screening for all newly diagnosed colorectal cancers. National guidelines and initiatives, including Healthy People 2020, included similar recommendations and cited the EGAPP and USPSTF recommendations. However, disparities in implementation based on race, ethnicity, and rural residence remain challenges. Public health achievements in promoting the evidence-based use of genomics for the prevention of hereditary cancers can inform future applications of genomics in public health.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/genética , Testes Genéticos , Neoplasias/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Centers for Disease Control and Prevention, U.S. , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Feminino , Genômica , Humanos , Neoplasias/diagnóstico , Neoplasias/patologia , Serviços Preventivos de Saúde , Saúde Pública , Estados UnidosRESUMO
PurposeWe examined 12-year trends in BRCA testing rates and costs in the context of clinical guidelines, national policies, and other factors.MethodsWe estimated trends in BRCA testing rates and costs from 2003 to 2014 for women aged 18-64 years using private claims data and publicly reported revenues from the primary BRCA testing provider.ResultsThe percentage of women with zero out-of-pocket payments for BRCA testing increased during 2013-2014, after 7 years of general decline, coinciding with a clarification of Affordable Care Act coverage of BRCA genetic testing. Beginning in 2007, family history accounted for an increasing proportion of women with BRCA tests compared with personal history, coinciding with BRCA testing guidelines for primary care settings and direct-to-consumer advertising campaigns. During 2013-2014, BRCA testing rates based on claims grew at a faster rate than revenues, following 3 years of similar growth, consistent with increased marketplace competition. In 2013, BRCA testing rates based on claims increased 57%, compared with 11% average annual increases over the preceding 3 years, coinciding with celebrity publicity.ConclusionThe observed trends in BRCA testing rates and costs are consistent with possible effects of several factors, including the Affordable Care Act, clinical guidelines and celebrity publicity.
Assuntos
Custos Diretos de Serviços , Genes BRCA1 , Genes BRCA2 , Testes Genéticos/economia , Testes Genéticos/métodos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Estados Unidos/epidemiologia , Adulto JovemRESUMO
In this paper, we review the evolution of the field of public health genomics in the United States in the past two decades. Public health genomics focuses on effective and responsible translation of genomic science into population health benefits. We discuss the relationship of the field to the core public health functions and essential services, review its evidentiary foundation, and provide examples of current US public health priorities and applications. We cite examples of publications to illustrate how Genetics in Medicine reflected the evolution of the field. We also reflect on how public-health genomics is contributing to the emergence of "precision public health" with near-term opportunities offered by the US Precision Medicine (AllofUs) Initiative.
Assuntos
Saúde Pública/tendências , Genômica/tendências , Humanos , Medicina de Precisão/tendências , Estados UnidosRESUMO
PURPOSE: We examined the utilization of precision medicine tests among Medicare beneficiaries through analysis of gene-specific tier 1 and 2 billing codes developed by the American Medical Association in 2012. METHODS: We conducted a retrospective cross-sectional study. The primary source of data was 2013 Medicare 100% fee-for-service claims. We identified claims billed for each laboratory test, the number of patients tested, expenditures, and the diagnostic codes indicated for testing. We analyzed variations in testing by patient demographics and region of the country. RESULTS: Pharmacogenetic tests were billed most frequently, accounting for 48% of the expenditures for new codes. The most common indications for testing were breast cancer, long-term use of medications, and disorders of lipid metabolism. There was underutilization of guideline-recommended tumor mutation tests (e.g., epidermal growth factor receptor) and substantial overutilization of a test discouraged by guidelines (methylenetetrahydrofolate reductase). Methodology-based tier 2 codes represented 15% of all claims billed with the new codes. The highest rate of testing per beneficiary was in Mississippi and the lowest rate was in Alaska. CONCLUSIONS: Gene-specific billing codes significantly improved our ability to conduct population-level research of precision medicine. Analysis of these data in conjunction with clinical records should be conducted to validate findings.Genet Med advance online publication 26 January 2017.
Assuntos
Testes Genéticos/estatística & dados numéricos , Medicare/estatística & dados numéricos , Idoso , Biomarcadores Tumorais , Estudos Transversais , Feminino , Predisposição Genética para Doença , Testes Genéticos/economia , Humanos , Formulário de Reclamação de Seguro/estatística & dados numéricos , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/economia , Medicina de Precisão/estatística & dados numéricos , Estudos Retrospectivos , Estados UnidosRESUMO
PURPOSE: We created an online knowledge base (the Public Health Genomics Knowledge Base (PHGKB)) to provide systematically curated and updated information that bridges population-based research on genomics with clinical and public health applications. METHODS: Weekly horizon scanning of a wide variety of online resources is used to retrieve relevant scientific publications, guidelines, and commentaries. After curation by domain experts, links are deposited into Web-based databases. RESULTS: PHGKB currently consists of nine component databases. Users can search the entire knowledge base or search one or more component databases directly and choose options for customizing the display of their search results. CONCLUSION: PHGKB offers researchers, policy makers, practitioners, and the general public a way to find information they need to understand the complicated landscape of genomics and population health.Genet Med 18 12, 1312-1314.
Assuntos
Bases de Dados Genéticas , Genômica , Bases de Conhecimento , Humanos , Internet , Saúde PúblicaRESUMO
PURPOSE: This overview systematically evaluates the clinical utility of using Oncotype DX and MammaPrint gene-expression profiling tests to direct treatment decisions in women with breast cancer. The findings are intended to inform an updated recommendation from the Evaluation of Genomic Applications in Practice and Prevention Working Group. METHODS: Evidence reported in systematic reviews evaluating the clinical utility of Oncotype DX and MammaPrint, as well as the ability to predict treatment outcomes, change in treatment decisions, and cost-effectiveness, was qualitatively synthesized. RESULTS: Five systematic reviews found no direct evidence of clinical utility for either test. Indirect evidence showed Oncotype DX was able to predict treatment effects of adjuvant chemotherapy, whereas no evidence of predictive value was found for MammaPrint. Both tests influenced a change in treatment recommendations in 21 to 74% of participants. The cost-effectiveness of Oncotype DX varied with the alternative compared. For MammaPrint, lack of evidence of the predictive value led to uncertainty in the cost-effectiveness. CONCLUSION: No studies were identified that provided direct evidence that using gene-expression profiling tests to direct treatment decisions improved outcomes in women with breast cancer. Three ongoing studies may provide direct evidence for determining the clinical utility of gene-expression profiling testing.
Assuntos
Neoplasias da Mama/genética , Perfilação da Expressão Gênica/métodos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Análise Custo-Benefício , Feminino , Perfilação da Expressão Gênica/economia , Humanos , Valor Preditivo dos Testes , Transcriptoma , Resultado do TratamentoRESUMO
PURPOSE: With the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field. METHODS: To pursue a discussion of the minimal elements needed to develop evidence-based guidelines in genomics, the Centers for Disease Control and Prevention and the National Cancer Institute jointly held a workshop to engage representatives from 35 organizations with interest in genomics (13 of which make recommendations). The workshop explored methods used in evidence synthesis and guideline development and initiated a dialogue to compare these methods and to assess whether they are consistent with the Institute of Medicine report "Clinical Practice Guidelines We Can Trust." RESULTS: The participating organizations that develop guidelines or recommendations all had policies to manage guideline development and group membership, and processes to address conflicts of interests. However, there was wide variation in the reliance on external reviews, regular updating of recommendations, and use of systematic reviews to assess the strength of scientific evidence. CONCLUSION: Ongoing efforts are required to establish criteria for guideline development in genomic medicine as proposed by the Institute of Medicine.
Assuntos
Medicina Baseada em Evidências , Genômica , Guias de Prática Clínica como Assunto , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/tendências , Genômica/métodos , Genômica/tendências , HumanosRESUMO
PURPOSE: The dizzying pace of genomic discoveries is leading to an increasing number of clinical applications. In this report, we provide a method for horizon scanning and 1 year data on translational research beyond bench to bedside to assess the validity, utility, implementation, and outcomes of such applications. METHODS: We compiled cross-sectional results of ongoing horizon scanning of translational genomic research, conducted between 16 May 2012 and 15 May 2013, based on a weekly, systematic query of PubMed. A set of 505 beyond bench to bedside articles were collected and classified, including 312 original research articles; 123 systematic and other reviews; 38 clinical guidelines, policies, and recommendations; and 32 articles describing tools, decision support, and educational materials. RESULTS: Most articles (62%) addressed a specific genomic test or other health application; almost half of these (n = 180) were related to cancer. We estimate that these publications account for 0.5% of reported human genomics and genetics research during the same time. CONCLUSION: These data provide baseline information to track the evolving knowledge base and gaps in genomic medicine. Continuous horizon scanning of the translational genomics literature is crucial for an evidence-based translation of genomics discoveries into improved health care and disease prevention.
Assuntos
Técnicas de Apoio para a Decisão , Medicina Baseada em Evidências , Genômica , Pesquisa Translacional Biomédica , Estudos Transversais , Humanos , Disseminação de Informação , Metanálise como AssuntoRESUMO
Three articles in this issue of Genetics in Medicine describe examples of "knowledge integration," involving methods for generating and synthesizing rapidly emerging information on health-related genomic technologies and engaging stakeholders around the evidence. Knowledge integration, the central process in translating genomic research, involves three closely related, iterative components: knowledge management, knowledge synthesis, and knowledge translation. Knowledge management is the ongoing process of obtaining, organizing, and displaying evolving evidence. For example, horizon scanning and "infoveillance" use emerging technologies to scan databases, registries, publications, and cyberspace for information on genomic applications. Knowledge synthesis is the process of conducting systematic reviews using a priori rules of evidence. For example, methods including meta-analysis, decision analysis, and modeling can be used to combine information from basic, clinical, and population research. Knowledge translation refers to stakeholder engagement and brokering to influence policy, guidelines and recommendations, as well as the research agenda to close knowledge gaps. The ultrarapid production of information requires adequate public and private resources for knowledge integration to support the evidence-based development of genomic medicine.
Assuntos
Genômica/métodos , Gestão do Conhecimento , Pesquisa Translacional Biomédica , Técnicas de Apoio para a Decisão , Medicina Baseada em Evidências , Humanos , Disseminação de Informação , Metanálise como Assunto , Projetos de Pesquisa , Literatura de Revisão como AssuntoRESUMO
A decade after the sequencing of the human genome, the National Human Genome Research Institute announced a strategic plan for genomic medicine. It calls for evaluating the structure and biology of genomes, understanding the biology of disease, advancing the science of medicine, and improving the effectiveness of health care. Fulfilling the promise of genomics urgently requires a population perspective to complement the bench-to-bedside model of translation. A population approach should assess the contribution of genomics to health in the context of social and environmental determinants of disease; evaluate genomic applications that may improve health care; design strategies for integrating genomics into practice; address ethical, legal, and social issues; and measure the population health impact of new technologies.
Assuntos
Genômica , Nível de Saúde , Pesquisa Translacional Biomédica , Atenção à Saúde , Genômica/organização & administração , Humanos , Pesquisa Translacional Biomédica/organização & administraçãoAssuntos
Aconselhamento Genético/estatística & dados numéricos , Testes Genéticos/estatística & dados numéricos , Genômica , Pré-Escolar , Feminino , Aconselhamento Genético/métodos , Aconselhamento Genético/normas , Testes Genéticos/normas , Genômica/métodos , Genômica/normas , Humanos , Recém-Nascido , Masculino , Futilidade Médica , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Gravidez , Medição de RiscoRESUMO
PURPOSE: The development of health-related genomic tests is decentralized and dynamic, involving government, academic, and commercial entities. Consequently, it is not easy to determine which tests are in development, currently available, or discontinued. We developed and assessed the usefulness of a systematic approach to identifying new genomic tests on the Internet. METHODS: We devised targeted queries of Web pages, newspaper articles, and blogs (Google Alerts) to identify new genomic tests. We finalized search and review procedures during a pilot phase that ended in March 2010. Queries continue to run daily and are compiled weekly; selected data are indexed in an online database, the Genomic Applications in Practice and Prevention Finder. RESULTS: After the pilot phase, our scan detected approximately two to three new genomic tests per week. Nearly two thirds of all tests (122/188, 65%) were related to cancer; only 6% were related to hereditary disorders. Although 88 (47%) of the tests, including 2 marketed directly to consumers, were commercially available, only 12 (6%) claimed United States Food and Drug Administration licensure. CONCLUSION: Systematic surveillance of the Internet provides information about genomic tests that can be used in combination with other resources to evaluate genomic tests. The Genomic Applications in Practice and Prevention Finder makes this information accessible to a wide group of stakeholders.
Assuntos
Testes Genéticos/métodos , Testes Genéticos/tendências , Genômica/métodos , Genômica/tendências , Internet , Ferramenta de Busca/métodos , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMO
Despite growing awareness about the potential for genomic information to improve population health, lingering communication challenges remain in describing the role of genomics in public health programs. Identifying and addressing these challenges provide an important opportunity for appropriate communication to ensure the translation of genomic discoveries for public health benefits. In this commentary, we describe 5 common communication challenges encountered by the Centers for Disease Control and Prevention's Office of Genomics and Precision Public Health based on over 20 years of experience in the field. These include (1) communicating that using genomics to assess rare diseases can have an impact on public health; (2) providing evidence that genetic factors can add important information to environmental, behavioral, and social determinants of health; (3) communicating that although genetic factors are nonmodifiable, they can increase the impact of public health programs and communication strategies; (4) addressing the concern that genomics is not ready for clinical practice; and (5) communicating that genomics is valuable beyond the domain of health care and can be integrated as part of public health programs. We discuss opportunities for addressing these communication challenges and provide examples of ongoing approaches to communication about the role of genomics in public health to the public, researchers, and practitioners.
Assuntos
Comunicação , Genômica , Saúde Pública , Centers for Disease Control and Prevention, U.S. , Atenção à Saúde , Humanos , Determinantes Sociais da Saúde , Estados UnidosRESUMO
Genetic tests are increasingly available for use in traditional clinical practice settings and through direct-to-consumer marketing. The need for evidence-based information and guidance on their appropriate use has never been more apparent. The independent Working Group of the Evaluation of Genomic Applications in Practice and Prevention Initiative commissions evidence-based reviews and develops recommendations to inform decision making surrounding the implementation of genetic tests and other applications of genomic technologies into clinical practice. A critical component of this analysis involves the identification and appropriate weighting of relevant health outcomes from genetic testing. Impacts of testing on morbidity and mortality are central considerations although research to document such outcomes can be challenging to conduct. In considering the broader impacts of genetic tests on the individual, familial and societal levels, psychosocial outcomes often take on increasing importance, and their systematic evaluation is a challenge for traditional methods of evidence-based review. Incorporating these types of outcomes in evidence-based processes is possible, however, and necessary to extract balanced and complete (or as complete as available data will allow) information on potential benefits and on potential harms. The framework used by the Evaluation of Genomic Applications in Practice and Prevention Working Group in considering, categorizing, and weighting health-related outcomes as applied to genomic technologies is presented here.
Assuntos
Medicina Baseada em Evidências/métodos , Testes Genéticos/métodos , Testes Genéticos/normas , Avaliação de Resultados em Cuidados de Saúde/métodos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Estudo de Associação Genômica Ampla/normas , Humanos , Programas Nacionais de Saúde , Medição de Risco , Fatores de Risco , Estados UnidosRESUMO
PURPOSE: To address the key question of whether using available "cardiogenomic profiles" leads to improved health outcomes (e.g., reduction in rates of myocardial infarction and stroke) and whether these profiles help in making medical or personal decisions. METHODS: A targeted evidence-based review based on published Evaluation of Genomic Applications in Practice and Prevention methodologies. RESULTS: No study addressed the overarching question directly. Evidence for the analytic validity of genomic profiles was inadequate for most genes (scale: convincing, adequate, and inadequate), but based on gray data, the analytic sensitivity and specificity might be adequate. For the 29 candidate genes (58 separate associations reviewed), the credibility of evidence for clinical validity was weak (34 associations) to moderate (23 associations), based on limited evidence, potential biases, and/or variability between included studies. The association of 9p21 variants with heart disease had strong credibility with odds ratios of 0.80 (95% confidence interval: 0.77-0.82) and 1.25 (95% confidence interval: 1.21-1.30), respectively, for individuals with no, or two, at-risk alleles versus those with one at-risk allele. Using a multiplicative model, we combined information from 24 markers predicting heart disease and from 13 markers for stroke. The areas under the curves (64.7% and 55.2%, respectively), and overall screening performance (detection rates of 24% and 14% at a 10% false-positive rate, respectively) do not warrant use as stand-alone tests. CONCLUSION: Even if genomic markers were independent of traditional risk factors, reports indicate that cardiovascular disease risk reclassification would be small. Improvement in health could occur with earlier initiation or higher adherence to medical or behavioral interventions, but no prospective studies documented such improvements (clinical utility).
Assuntos
Doenças Cardiovasculares/genética , Doenças Cardiovasculares/prevenção & controle , Marcadores Genéticos/genética , Medição de Risco , Testes Genéticos , Estudo de Associação Genômica Ampla , Humanos , Avaliação de Processos e Resultados em Cuidados de Saúde , Reprodutibilidade dos TestesRESUMO
Cascade testing is the process of offering genetic counseling and testing to at-risk relatives of an individual who has been diagnosed with a genetic condition. It is critical for increasing the identification rates of individuals with these conditions and the uptake of appropriate preventive health services. The process of cascade testing is highly varied in clinical practice, and a comprehensive understanding of factors that hinder or enhance its implementation is necessary to improve this process. We conducted a systematic review to identify barriers and facilitators for cascade testing and searched PubMed, CINAHL via EBSCO, Web of Science, EMBASE, and the Cochrane Library for articles published from the databases' inception to November 2018. Thirty articles met inclusion criteria. Barriers and facilitators identified from these studies at the individual-level were organized into the following categories: (1) demographics, (2) knowledge, (3) attitudes, beliefs, and emotional responses of the individual, and (4) perceptions of relatives, relatives' responses, and attitudes toward relatives. At the interpersonal-level, barriers and facilitators were categorized as (1) family communication-, support- and dynamics-, and (2) provider-factors. Finally, barriers at the environmental-level relating to accessibility of genetic services were also identified. Our findings suggest that several individual, interpersonal and environmental factors may play a role in cascade testing. Future studies to further investigate these barriers and facilitators are needed to inform future interventions for improving the implementation of cascade testing for genetic conditions in clinical practice.
Assuntos
Aconselhamento Genético/métodos , Testes Genéticos/métodos , Conhecimentos, Atitudes e Prática em Saúde , Participação do Paciente/psicologia , Utilização de Instalações e Serviços/estatística & dados numéricos , Família/psicologia , Aconselhamento Genético/psicologia , Humanos , Facilitação SocialRESUMO
BACKGROUND: Although uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be. METHODS: The MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65-0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40-60 years), end age (70-85 years), and interval (1-20 years). RESULTS: With current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40-80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation. CONCLUSIONS: Currently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening.