Population-wide Screening Programs Research Articles

Evaluating and mapping the evidence that screening for diabetic foot disease meets the criteria for population-wide screening: a scoping review

ObjectiveTo evaluate and map the evidence around diabetes-related foot screening using the World Health Organisation screening principles, which set the gold standard for determining the appropriateness of introducing population-wide screening...

A Multi-Stage Approach for Cardiovascular Risk Assessment from Retinal Images Using an Amalgamation of Deep Learning and Computer Vision Techniques.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. Early detection and effective risk assessment are crucial for implementing preventive measures and improving patient outcomes for CVDs. This work presents a novel approach to CVD risk assessment using fundus images, leveraging the inherent connection between retinal microvascular changes and systemic vascular health. This study aims to develop a predictive model for the early detection of CVDs by evaluating retinal vascular parameters. This methodology integrates both handcrafted features derived through mathematical computation and retinal vascular patterns extracted by artificial intelligence (AI) models. By combining these approaches, we seek to enhance the accuracy and reliability of CVD risk prediction in individuals. The methodology integrates state-of-the-art computer vision algorithms and AI techniques in a multi-stage architecture to extract relevant features from retinal fundus images. These features encompass a range of vascular parameters, including vessel caliber, tortuosity, and branching patterns. Additionally, a deep learning (DL)-based binary classification model is incorporated to enhance predictive accuracy. A dataset comprising fundus images and comprehensive metadata from the clinical trials conducted is utilized for training and validation. The proposed approach demonstrates promising results in the early prediction of CVD risk factors. The interpretability of the approach is enhanced through visualization techniques that highlight the regions of interest within the fundus images that are contributing to the risk predictions. Furthermore, the validation conducted in the clinical trials and the performance analysis of the proposed approach shows the potential to provide early and accurate predictions. The proposed system not only aids in risk stratification but also serves as a valuable tool for identifying vascular abnormalities that may precede overt cardiovascular events. The approach has achieved an accuracy of 85% and the findings of this study underscore the feasibility and efficacy of leveraging fundus images for cardiovascular risk assessment. As a non-invasive and cost-effective modality, fundus image analysis presents a scalable solution for population-wide screening programs. This research contributes to the evolving landscape of precision medicine by providing an innovative tool for proactive cardiovascular health management. Future work will focus on refining the solution's robustness, exploring additional risk factors, and validating its performance in additional and diverse clinical settings.

Why selective screening for asymptomatic carotid stenosis is currently appropriate: a special report.

Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Measuring Costs of Cardiovascular Disease Prevention for Patients with Familial Hypercholesterolemia in Administrative Claims Data.

Familial hypercholesterolemia is a common genetic condition that significantly increases an individual's risk of cardiovascular events such as heart attack, stroke, and cardiac death and is a candidate for population-wide screening programs. Economic analyses of strategies to identify and treat familial hypercholesterolemia are limited by a lack of real-world cost estimates for screening services and medications for reducing cardiovascular risk in this population. We estimated the cost of lipid panel testing in patients with hyperlipidemia and the cost of statins, ezetimibe, and PCKS9 inhibitors in patients with familial hypercholesterolemia from a commercial claims database and report costs and charges per panel and prescription by days' supply. The mean cost for a 90-day supply for statins was $183.33, 2.3 times the mean cost for a 30-day supply at $79.35. PCSK9 inhibitors generated the highest mean costs among medications used by patients with familial hypercholesterolemia. Lipid testing and lipid-lowering medications for cardiovascular disease prevention generate substantial real-world costs which can be used to improve cost-effectiveness models of familial hypercholesterolemia screening and care management.

Use of a multi-phased approach to identify and address facilitators and barriers to the implementation of a population-wide genomic screening program

IntroductionPopulation-wide genomic screening for CDC Tier-1 conditions offers the ability to identify the 1–2% of the US population at increased risk for Hereditary Breast and Ovarian Cancer, Lynch Syndrome, and Familial Hypercholesterolemia. Implementation of population-wide screening programs is highly complex, requiring engagement of diverse collaborators and implementation teams. Implementation science offers tools to promote integration of these programs through the identification of determinants of success and strategies to address potential barriers.MethodsPrior to launching the program, we conducted a pre-implementation survey to assess anticipated barriers and facilitators to reach, effectiveness, adoption, implementation, and maintenance (RE-AIM), among 51 work group members (phase 1). During the first year of program implementation, we completed coding of 40 work group meetings guided by the Consolidated Framework for Implementation Research (CFIR) (phase 2). We matched the top barriers to implementation strategies identified during phase 2 using the CFIR-ERIC (Expert Recommendation for Implementing Change) matching tool.ResultsStaffing and workload concerns were listed as the top barrier in the pre-implementation phase of the program. Top barriers during implementation included adaptability (n = 8, 20%), complexity (n = 14, 35%), patient needs and resources (n = 9, 22.5%), compatibility (n = 11, 27.5%), and self-efficacy (n = 9, 22.5%). We identified 16 potential implementation strategies across six ERIC clusters to address these barriers and operationalized these strategies for our specific setting and program needs.ConclusionOur findings provide an example of successful use of the CFIR-ERIC tool to guide implementation of a population-wide genomic screening program.

Social determinants and participation in fecal occult blood test based colorectal cancer screening: A qualitative systematic review and meta-synthesis.

Colorectal cancer (CRC) screening through fecal occult blood testing (FOBT) has saved thousands of lives globally with multiple countries adopting comprehensive population wide screening programs. Participation rates in FOBT based CRC screening for the socially and economically disadvantaged remains low. The aim of this systematic review is to explore empirical evidence that will guide targeted interventions to improve participation rates within priority populations. PubMed, Embase, Scopus, Cinahl and PsycInfo were systematically searched from inception to 22 June 2022. Eligible studies contained qualitative evidence identifying barriers to FOBT based CRC screening for populations impacted by the social determinants of health. An inductive thematic synthesis approach was applied using grounded theory methodology, to explore descriptive themes and interpret these into higher order analytical constructs and theories. A total of 8,501 publications were identified and screened. A total of 48 studies from 10 countries were eligible for inclusion, representing 2,232 subjects. Coding within included studies resulted in 30 key descriptive themes with a thematic frequency greater than 10%. Coded themes applied to four overarching, interconnected barriers driving inequality for priority populations: social, behavioural, economic and technical/interfaces. SO WHAT?: This study has highlighted the need for stronger patient/provider relationships to mitigate barriers to FOBT screening participation for diverse groups. Findings can assist health professionals and policy makers address the systemic exclusion of priority populations in cancer screening by moving beyond the responsibility of the individual to a focus on addressing the information asymmetry driving low value perceptions.

BMPR2 as a Novel Predisposition Gene for Hereditary Colorectal Polyposis

Colorectal cancer (CRC) is one of the most prevalent tumors worldwide, with incidence quickly increasing (particularly in the context of early-onset cases), despite important prevention efforts, mainly in the form of population-wide screening programs. Although many cases present a clear familial component, the current list of hereditary CRC genes leaves a considerable proportion of the cases unexplained. In this work, we used whole-exome sequencing approaches on 19 unrelated patients with unexplained colonic polyposis to identify candidate CRC predisposition genes. The candidate genes were then validated in an additional series of 365 patients. CRISPR-Cas9 models were used to validate BMPR2 as a potential candidate for CRC risk. We found 8 individuals carrying 6 different variants in the BMPR2 gene (approximately 2% of our cohort of patients with unexplained colonic polyposis). CRISPR-Cas9 models of 3 of these variants showed that the p.(Asn442Thrfs∗32) truncating variant completely abrogated BMP pathway function in a similar way to the BMPR2 knockout. Missense variants p.(Asn565Ser), p.(Ser967Pro) had varying effects on cell proliferation levels, with the former impairing cell control inhibition via noncanonical pathways. Collectively, these results support loss-of-function BMPR2 variants as candidates to be involved in CRC germline predisposition.

Twenty-Five Years of Contemplating Genotype-Based Hereditary Hemochromatosis Population Screening.

Hereditary hemochromatosis (HH) is a rather frequent, preventable disease because the progressive iron overload affecting many organs can be effectively reduced by phlebotomy. Even before the discovery of the major gene, HFE, in 1996, hemochromatosis was seen as a candidate for population-wide screening programmes. A US Centers of Disease Control and the National Human Genome Research Institute expert panel convened in 1997 to consider genotype-based HH population-wide screening and decided that the scientific evidence available at that time was insufficient and advised against. In spite of a large number of studies performed within the last 25 years, addressing all aspects of HH natural history, health economics, and social acceptability, no professional body worldwide has reverted this decision, and HH remains a life-threatening condition that often goes undetected at a curable stage.

Etiologies of Melanoma Development and Prevention Measures: A Review of the Current Evidence.

Simple SummaryMelanoma constitutes a major public health risk, with the rates of diagnosis increasing on a yearly basis. Monitoring for risk factors and preventing dangerous behaviors that increase melanoma risk, such as tanning, are important measures for melanoma prevention. Additionally, assessing the effectiveness of various methods to prevent sun exposure and sunburns—which can lead to melanoma—is important to help identify ways to reduce the development of melanoma. We summarize the recent evidence regarding the heritable and behavioral risks underlying melanoma, as well as the current methods used to reduce the risk of developing melanoma and to improve the diagnosis of this disease.(1) Melanoma is the most aggressive dermatologic malignancy, with an estimated 106,110 new cases to be diagnosed in 2021. The annual incidence rates continue to climb, which underscores the critical importance of improving the methods to prevent this disease. The interventions to assist with melanoma prevention vary and typically include measures such as UV avoidance and the use of protective clothing, sunscreen, and other chemopreventive agents. However, the evidence is mixed surrounding the use of these and other interventions. This review discusses the heritable etiologies underlying melanoma development before delving into the data surrounding the preventive methods highlighted above. (2) A comprehensive literature review was performed to identify the clinical trials, observational studies, and meta-analyses pertinent to melanoma prevention and incidence. Online resources were queried to identify epidemiologic and clinical trial information. (3) Evidence exists to support population-wide screening programs, the proper use of sunscreen, and community-targeted measures in the prevention of melanoma. Clinical evidence for the majority of the proposed preventive chemotherapeutics is presently minimal but continues to evolve. (4) Further study of these chemotherapeutics, as well as improvement of techniques in artificial intelligence and imaging techniques for melanoma screening, is warranted for continued improvement of melanoma prevention.

Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

BackgroundVitamin D has been identified as a potential protective factor in the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally.MethodsIn this ecological study, a series of linear and polynomial regression tests were performed between country-specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps.ResultsThe inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates.ConclusionThe age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.

The impact of information about different absolute benefits and harms on intention to participate in colorectal cancer screening: A think-aloud study and online randomised experiment.

BackgroundThere is considerable heterogeneity in individuals’ risk of disease and thus the absolute benefits and harms of population-wide screening programmes. Using colorectal cancer (CRC) screening as an exemplar, we explored how people make decisions about screening when presented with information about absolute benefits and harms, and how those preferences vary with baseline risk, between screening tests and between individuals.MethodWe conducted two linked studies with members of the public: a think-aloud study exploring decision making in-depth and an online randomised experiment quantifying preferences. In both, participants completed a web-based survey including information about three screening tests (colonoscopy, sigmoidoscopy, and faecal immunochemical testing) and then up to nine scenarios comparing screening to no screening for three levels of baseline risk (1%, 3% and 5% over 15 years) and the three screening tests. Participants reported, after each scenario, whether they would opt for screening (yes/no).ResultsOf the 20 participants in the think-aloud study 13 did not consider absolute benefits or harms when making decisions concerning CRC screening. In the online experiment (n = 978), 60% expressed intention to attend at 1% risk of CRC, 70% at 3% and 77% at 5%, with no differences between screening tests. At an individual level, 535 (54.7%) would attend at all three risk levels and 178 (18.2%) at none. The 27% whose intention varied by baseline risk were more likely to be younger, without a family history of CRC, and without a prior history of screening.ConclusionsMost people in our population were not influenced by the range of absolute benefits and harms associated with CRC screening presented. For an appreciable minority, however, magnitude of benefit was important.

Reference intervals of spot urine copper excretion in preschool children and potential application in pre-symptomatic screening of Wilson disease

The objectives were to determine the reference intervals of spot urine copper excretion indexes in pre-school children and to evaluate their utility in screening for Wilson disease (WD). With spot urine collected from a control sample of preschool children (aged 3-7 years, n=153), the reference intervals of spot urine copper excretion indexes and their biological variation were defined. In order to investigate their utility performance in screening for WD in this age group, multiple spot urine samples from six WD patients who were diagnosed at presymptomatic stage were also analysed and compared. Cut-off values useful for detection of WD were defined by receiver operator curve (ROC) analysis. Biological (inter-individual) variation of spot urine copper indexes expressed as coefficient of variation (CVg) were around 60% at this age group, which was moderate and similar to other clinically useful urine tests, such as urine albumin excretion ratio. Spot urine copper excretion strongly correlated with both urine creatinine and osmolality. Linear regression against both creatinine and osmolality showed that ∼94% of data points in healthy preschool children fell within the prediction interval, suggesting that both were useful normalisation factors. ROC showed that copper to osmolality ratio was the best index with an area under curve (AUC) greater than 0.98. Cut-off values of 0.5 μmol/L, 0.1 μmol/mmol and 0.00085 μmol/mOsmol (32 μg/L, 56 μg/g creatinine and 0.054 μg/mOsmol, respectively, in conventional units) for spot urine copper concentration, copper to creatinine ratio and copper to osmolality ratio, respectively, have potential application in the differentiation of WD patients. Based on the data, a new WD screening strategy targeting preschool children is proposed. Application of a bivariate screening strategy using spot urine copper concentration and urine osmolality may be useful in a population-wide screening program for WD among preschool children.

Biobanking in Molecular Biomarker Research for the Early Detection of Cancer

Although population-wide screening programs for several cancer types have been implemented in multiple countries, screening procedures are invasive, time-consuming and often perceived as a burden for patients. Molecular biomarkers measurable in non-invasively collected samples (liquid biopsies) could facilitate screening, as they could have incremental value on early diagnosis of cancer, but could also predict prognosis or monitor treatment response. Although the shift towards biomarkers from liquid biopsies for early cancer detection was initiated some time ago, there are many challenges that hamper the development of such biomarkers. One of these challenges is large-scale validation that requires large prospectively collected biobanks with liquid biopsies. Establishing those biobanks involves several considerations, such as standardization of sample collection, processing and storage within and between biobanks. In this perspective, we will elaborate on several issues that need to be contemplated in biobanking, both in general and for certain specimen types specifically, to be able to facilitate biomarker validation for early detection of cancer.

The interplay of sun damage and genetic risk in Australian multiple and single primary melanoma cases and controls.

Skin phenotype, host genotype and ultraviolet (UV) damage play a role in the development of melanoma. To ascertain whether the level of UV damage at the site of melanomas was associated with genetic polymorphisms. Deep phenotyping was performed on 1244 individuals; 281 with multiple primary melanomas (MPMs), 304 with single primary melanoma (SPM) and 659 convenience controls. Genotype data was generated using the Illumina CoreExome microarray platform, assaying over 500000 single-nucleotide polymorphisms. A subset of variants were combined to assess a polygenic risk score (PRS) for melanoma. Most MPM cases were diagnosed in patients aged > 40 years, in sites with visible chronic UV damage. Women and those diagnosed at age ≤ 40 years were less likely to have perilesional UV damage. Patients with MPM had higher frequencies of MITF E318K, MC1R R-alleles and the ASIP risk haplotype. Individuals who had melanoma in a visibly UV-damaged site were more likely to carry MC1R rs75570604 [odds ratio (OR) 2·5], 9q31.2 rs10816595 (OR 1·4) and MTAP rs869329 (OR 1·4). These same alleles were more common in patients with MPM who were diagnosed at age ≤ 40 years. The mean PRS was significantly higher in MPM than in SPM and controls. Naevus count was comparable in early-onset MPM cases and those diagnosed at age > 40 years. Our cohort demonstrated higher frequencies of previously reported alleles associated with melanoma. MPM melanomas more commonly occur in UV-damaged areas, and these individuals are more likely to carry MC1R red hair colour alleles. Awareness of the interplay of genetic vulnerability with UV damage can stratify risk and guide recommendations for melanoma screening. What's already known about this topic? Skin phenotype, host genotype and ultraviolet (UV) damage all play a role in melanoma development. One of the main risk factors is a personal history of melanoma; second and subsequent primary melanomas account for over 20% of all melanomas registered in Queensland. Multiple loci are associated with melanoma risk, including many low-penetrance loci, which may have a cumulatively significant risk. Population-wide screening programmes for melanoma are not yet economically viable. What does this study add? Patients diagnosed with melanoma at age ≤ 40 years were more likely than older patients to have melanomas in non-UV-damaged sites. Patients with multiple melanomas had higher frequencies of MITF E318K, MC1R R-alleles, and the ASIP extended risk haplotype than patients with single melanoma. CDKN2A, MC1R and MTAP variants were more frequent in patients who developed melanomas at a younger age, but also in those whose melanomas were all on visibly UV-damaged sites. What is the translational message? Incorporating these genetic findings into the known risk factors of skin phenotype and visible UV damage may allow for a more customized and economically feasible approach to early detection of melanoma, particularly in younger patients. Plain language summary available online.

A more effective approach to lung cancer screening?

A more effective approach to lung cancer screening?

Gastric Cancer – From Aetiology to Management: Differences Between the East and the West

Gastric cancers are highly prevalent in both the East and the West, although they differ in aetiology and prognostic outcome. Management of gastric cancer from screening to definitive treatment varies substantially between Eastern and Western countries and regions, owing to numerous factors, including government incentives to carry out population-wide screening programmes to detect early disease, differences in clinical and biological tumour behaviours and responsiveness to treatment, patient accessibility to effective treatment, etc. This review highlights and contrasts the differences in tumour aetiology and histology, as well as the management approaches between the East and the West, which gives important insights and inspirations on future international multicentre research collaboration to combat this dreadful malignancy.

Optimal population screening policies for Alzheimer’s disease*

Alzheimer’s disease (AD) constitutes a serious societal healthcare issue as the proportion of the aging population increases. There are ongoing discussions about the necessity of screening the population for AD. We investigate optimal population screening policies for AD using Markov Decision Processes (MDPs). The objective function combines quality-adjusted life years and costs. The disease states are identified according to Clinical Dementia Rating (CDR) scores. The screening test in the model is the Mini Mental State Examination (MMSE), a cognitive test that is widely used in clinical practice. A numerical implementation of the MDP model is presented based on data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and existing literature. In the baseline case, the optimal outcome is not to employ a population-wide screening program. We conduct extensive sensitivity analyses on several model parameters. Our study reveals that the optimal policy may be sensitive to changes in transition probability estimates. When we focus on transitions that are related to treatment effectiveness, we find that implementing a population screening policy becomes socially optimal when plans that lead to cognitive ability stabilization or improvement become available.

Trends of Colorectal Cancer Incidence in Thailand by Age, Gender, and Region

Background: Colorectal cancer (CRC) is the third most common cancer in the world. While CRC incidence has decreased in many western countries over the last decades, largely thanks to screening, it is increasing in low and middle-income countries, including Thailand. However, it is unclear if these increases are consistent across different regions, gender and age groups. Aim: To understand the age-, gender- and region-specific temporal variation in CRC incidence in Thailand since the 1990s. Methods: We analyzed CRC incidence data from the Thailand National Cancer Network (TCIN) cancer registries, which include Chiang Mai (1990-2012), Lampang (1993-2014), Lopburi (2000-2014), Khon Kaen (1990-2014) and Songkhla (1990-2014) cancer registries. Trends in age-adjusted incidence (measured by annual percentage change (APC)) were assessed using Joinpoint regression. Trends by birth-year and calendar-year were assessed using age-period-cohort models. All analyses were done by region, gender, and age group (30-49, 50-84, 30-84). Results: CRC incidence has been increasing significantly in all regions, gender, and age groups; Overall, the APC was 3.82 for men and 3.84 for women (Chiang Mai, 4.34 for men & 3.26 for women; Khon Kaen, 2.69 for men & 3.68 for women; Lampang, 2.13 for men & 3.37 for women; Lopburi, 5.31 for men & 4.67 for women; Songkhla, 4.67 for men & 4.32 for women). The increase in incidence was higher for ages 50-84 (APC = 3.99 for men & 4.04 for women) compared with ages 30-49 (APC=2.97 for men & 3.09 for women). Test of parallelism suggests that increases are consistent between gender (P-value=0.97). The age-period-cohort analysis suggests that both calendar-year and birth-year are strongly correlated with CRC incidence trends, with a stronger relationship with birth-year than calendar-year for both genders. Conclusion: In contrast to western countries such as the US, CRC incidence is increasing across all age groups in Thailand, with faster increase in older ages. This highlights the needs for establishing population-wide screening programs to reduce the burden and stop the rise of CRC in Thailand and low-middle income countries.

A new approach to epigenome-wide discovery of non-invasive methylation biomarkers for colorectal cancer screening in circulating cell-free DNA using pooled samples

BackgroundColorectal cancer is the fourth cause of cancer-related deaths worldwide, though detection at early stages associates with good prognosis. Thus, there is a clear demand for novel non-invasive tests for the early detection of colorectal cancer and premalignant advanced adenomas, to be used in population-wide screening programs. Aberrant DNA methylation detected in liquid biopsies, such as serum circulating cell-free DNA (cfDNA), is a promising source of non-invasive biomarkers. This study aimed to assess the feasibility of using cfDNA pooled samples to identify potential serum methylation biomarkers for the detection of advanced colorectal neoplasia (colorectal cancer or advanced adenomas) using microarray-based technology.ResultscfDNA was extracted from serum samples from 20 individuals with no colorectal findings, 20 patients with advanced adenomas, and 20 patients with colorectal cancer (stages I and II). Two pooled samples were prepared for each pathological group using equal amounts of cfDNA from 10 individuals, sex-, age-, and recruitment hospital-matched. We measured the methylation levels of 866,836 CpG positions across the genome using the MethylationEPIC array. Pooled serum cfDNA methylation data meets the quality requirements. The proportion of detected CpG in all pools (> 99% with detection p value < 0.01) exceeded Illumina Infinium methylation data quality metrics of the number of sites detected. The differential methylation analysis revealed 1384 CpG sites (5% false discovery rate) with at least 10% difference in the methylation level between no colorectal findings controls and advanced neoplasia, the majority of which were hypomethylated. Unsupervised clustering showed that cfDNA methylation patterns can distinguish advanced neoplasia from healthy controls, as well as separate tumor tissue from healthy mucosa in an independent dataset. We also observed that advanced adenomas and stage I/II colorectal cancer methylation profiles, grouped as advanced neoplasia, are largely homogenous and clustered close together.ConclusionsThis preliminary study shows the viability of microarray-based methylation biomarker discovery using pooled serum cfDNA samples as an alternative approach to tissue specimens. Our strategy sets an open door for deciphering new non-invasive biomarkers not only for colorectal cancer detection, but also for other types of cancers.

Disability and participation in breast and bowel cancer screening in England: a large prospective study

Background:There is limited information about participation in organised population-wide screening programmes by people with disabilities.Methods:Data from the National Health Service routine screening programmes in England were linked to information on disability reported by the Million Women Study cohort participants.Results:Of the 473 185 women offered routine breast or bowel cancer screening, 23% reported some disability. Women with disabilities were less likely than other women to participate in breast cancer screening (RR=0.64, 95% CI: 0.62–0.65) and in bowel cancer screening (RR=0.75, 0.73–0.76). Difficulties with self-care or vision were associated with the greatest reduction in screening participation.Conclusion:Participation in routine cancer screening programmes in England is reduced in people with disabilities and participation varies by type of disability.