Population-level impact of the BMJ Rapid Recommendation for colorectal cancer screening: a microsimulation analysis.

OBJECTIVE: In 2019, a BMJ Rapid Recommendation advised against colorectal cancer (CRC) screening for adults with a predicted 15-year CRC risk below 3%. Using Switzerland as a case study, we estimated the population-level impact of this recommendation. DESIGN: We predicted the CRC risk of all respondents to the population-based Swiss Health Survey. We derived the distribution of risk-based screening start age, assuming predicted risk was calculated every 5 years between ages 25 and 70 and screening started when this risk exceeded 3%. Next, the MISCAN-Colon microsimulation model evaluated biennial faecal immunochemical test (FIT) screening with this risk-based start age. As a comparison, we simulated screening initiation based on age and sex. RESULTS: Starting screening only when predicted risk exceeded 3% meant 82% of women and 90% of men would not start screening before age 65 and 60, respectively. This would require 43%-57% fewer tests, result in 8%-16% fewer CRC deaths prevented and yield 19%-33% fewer lifeyears gained compared with screening from age 50. Screening women from age 65 and men from age 60 had a similar impact as screening only when predicted risk exceeded 3%. CONCLUSION: With the recommended risk prediction tool, the population impact of the BMJ Rapid Recommendation would be similar to screening initiation based on age and sex only. It would delay screening initiation by 10-15 years. Although halving the screening burdens, screening benefits would be reduced substantially compared with screening initiation at age 50. This suggests that the 3% risk threshold to start CRC screening might be too high.

Costs and Projected Effect of a Federally Qualified Health Center-Based Mailed Colorectal Cancer Screening Program in Texas.

Introduction: Mailed stool testing for colorectal cancer (CRC) may improve screening uptake and reduce the incidence and mortality of CRC, especially among patients at federally qualified health centers (FQHCs). To expand screening programs it is important to identify cost-effective approaches. Methods: We developed a decision-analytic model to estimate the cost, effects on screening and patient outcomes (CRCs detected, CRCs prevented, CRC deaths prevented), and cost-effectiveness of implementing a state-wide mailed stool testing program over 5 years among unscreened, age-eligible (aged 50-75 y) patients at FQHCs in Texas. We compared various outreach strategies and organizational structures (centralized, regional, or a hybrid). We used data from our existing regional mailed stool testing program and recent systematic reviews to set parameters for the model. Costs included start-up and ongoing activities and were estimated in 2022 US dollars from the perspective of a hypothetical third-party payer. Cost-effectiveness was assessed by using both incremental and average cost-effectiveness ratios. Results: Using either a statewide centralized or hybrid organizational configuration to mail stool tests to newly eligible FQHC patients and patients who have responded at least once since program inception is likely to result in the best use of resources over 5 years, enabling more than 110,000 additional screens, detecting an incremental 181 to 194 CRCs, preventing 91 to 98 CRCs, and averting 46 to 50 CRC deaths, at a cost of $10 million to $11 million compared with no program. Conclusions: A statewide mailed stool testing program for FQHC patients can be implemented at reasonable cost with considerable effects on CRC screening outcomes, especially when its structure maximizes program efficiency while maintaining effectiveness.

Oxidative balance score: a potential tool for reducing the risk of colorectal cancer and its subsites incidences.

Background: The Oxidative Balance Score (OBS) is commonly used to assess oxidative stress and provides a comprehensive evaluation of dietary and lifestyle-related exposures. However, there is limited research on the association between OBS and colorectal cancer (CRC), its subsites, and complications. The objective of this study was to assess the relationship between OBS and the risk of CRC, its subsites, and common complications in a large prospective cohort study. Methods: We included data from 175,808 participants in the UK Biobank data sample repository from 2006 to 2010. We evaluated OBS using a scoring system based on 22 dietary and lifestyle factors. Multiple adjustments, including multivariate Cox proportional hazard regression, gender stratification, subgroup analysis, and sensitivity analysis, were performed to fully explore the relationship between OBS and CRC, its subsites, and complications. The mediation analysis was conducted to investigate whether serum albumin, uric acid, and neutrophil levels mediate the relationship between OBS and CRC. Results: After adjusting for potential confounding factors, a significant negative correlation was found between OBS and the risk of CRC and its subsites (proximal colon cancer, distal colon cancer, and rectal cancer). This correlation was particularly pronounced in male CRC patients. Serum albumin, uric acid, and neutrophil count, which are biomarkers, were found to have a significant mediating effect between OBS and CRC. Conclusion: Our study suggests that higher exposure to antioxidants assessed through OBS (diet and lifestyle rich in antioxidants) may decrease the occurrence of CRC and its subsites.

Berberine: Potential preventive and therapeutic strategies for human colorectal cancer.

Colorectal cancer (CRC) is a common digestive tract tumor, with incidences continuing to rise. Although modern medicine has extended the survival time of CRC patients, its adverse effects and the financial burden cannot be ignored. CRC is a multi-step process and can be caused by the disturbance of gut microbiome and chronic inflammation's stimulation. Additionally, the presence of precancerous lesions is also a risk factor for CRC. Consequently, scientists are increasingly interested in identifying multi-target, safe, and economical herbal medicine and natural products. This paper summarizes berberine's (BBR) regulatory mechanisms in the occurrence and development of CRC. The findings indicate that BBR regulates gut microbiome homeostasis and controls mucosal inflammation to prevent CRC. In the CRC stage, BBR inhibits cell proliferation, invasion, and metastasis, blocks the cell cycle, induces cell apoptosis, regulates cell metabolism, inhibits angiogenesis, and enhances chemosensitivity. BBR plays a role in the overall management of CRC. Therefore, using BBR as an adjunct to CRC prevention and treatment could become a future trend in oncology.

[Zinc Suppresses Colorectal Cancer Development through Cell-mediated Immunity].

Zinc is one of the essential trace elements, and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the effect of zinc on colorectal cancer and its mechanisms. Mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) to develop colorectal cancer, then the relationship between zinc content in the diet and the number and area of tumors in the colon was observed. The number of tumors in the colon was significantly higher in the no-zinc-added diet group compared to the normal zinc intake group, and about half the number in the high-zinc-intake group compared to the normal-zinc-intake group. In T-cell-deficient mice, the number of tumors in the high-zinc-intake group was similar to that in the normal-zinc-intake group, suggesting that the inhibitory effect of zinc was dependent on T cells. Furthermore, we found that the amount of granzyme B transcript released by cytotoxic T cells upon antigen stimulation was significantly increased by the addition of zinc. We also showed that granzyme B transcriptional activation by zinc addition was dependent on calcineurin activity. Collectively, we have shown that zinc exerts its tumor-suppressive effect by acting on cytotoxic T cells, the center of cellular immunity, and that it increases the transcription of granzyme B, one of the key molecules involved in tumor immunity. In this symposium, we would like to introduce our latest data on the relationship between zinc and tumor immunity.

Non-preventable cases of breast, prostate, lung, and colorectal cancer in 2050 in an elimination scenario of modifiable risk factors.

Most Western countries have increasing number of new cancer cases per year. Cancer incidence is primarily influenced by basically avoidable risk factors and an aging population. Through hypothetical elimination scenarios of multiple major risk factors for cancer, we estimated the number of new cancer cases that are non-preventable in 2050. We compare numbers of new postmenopausal breast, prostate, lung, and colorectal cancer cases in 2021 to projected numbers of new cases in 2050 under prevention scenarios regarding smoking, overweight and obesity, and alcohol consumption: no intervention, 50%, and 100% instant reduction. Cancer incidence data were derived from NORDCAN, and risk factor prevalence data from the Danish National Health Survey. Cancer projections were calculated with the Prevent program. Hypothetical 100% instant elimination of major risk factors for cancer in Denmark in 2022 will result in unchanged numbers of new breast and colorectal cancers in 2050. The number of new prostate cancers will increase by 25% compared to 2021. Unchanged risk factor levels will result in noticeable increase in cancer burden. Increase in life expectancy and age will entail an increase in cancer incidence, despite maximum effect of preventive actions in the population. Our results are important when planning future health care.

Screening for Colorectal Cancer.

Colorectal cancer remains the third leading cause of cancer death in the United States. Colorectal cancer screening allows for prevention and early detection of precancerous and cancerous lesions, and screening has been shown to be effective in preventing colorectal cancer deaths. Screening recommendations vary by patient risk profile. A variety of screening modalities exist.

External validation of the colorectal cancer risk score LiFeCRC using food frequency questions in the HUNT study.

PURPOSE: To mitigate the increasing colorectal cancer (CRC) incidence globally and prevent CRC at the individual level, individual lifestyle information needs to be easily translated into CRC risk assessment. Several CRC risk prediction models exist and their clinical usefulness depends on their ease of use. Our objectives were to assess and externally validate the LiFeCRC score in our independent, unselected population and to investigate the use of simpler food frequency measurements in the score. METHODS: Incidental colon and rectal cancer cases were compared to the general population among 78,580 individuals participating in a longitudinal health study in Norway (HUNT). Vegetable, dairy product, processed meat and sugar/confectionary consumption was scored based on food frequency. The LiFeCRC risk score was calculated for each individual. RESULTS: Over a median of 10 years following participation in HUNT, colon cancer was diagnosed in 1355 patients and rectal cancer was diagnosed in 473 patients. The LiFeCRC score using food frequencies demonstrated good discrimination in CRC overall (AUC 0.77) and in sex-specific models (AUC men 0.76 and women 0.77) in this population also including individuals ≥ 70 years and patients with diabetes. It performed somewhat better in colon (AUC 0.80) than in rectal cancer (AUC 0.72) and worked best for female colon cancer (AUC 0.81). CONCLUSION: Readily available clinical variables and food frequency questions in a modified LiFeCRC score can identify patients at risk of CRC and may improve primary prevention by motivating to lifestyle change or participation in the CRC screening programme.

Barriers to the use of tests for early detection of colorectal cancer in Chile.

This study aimed to assess the use of colorectal cancer (CRC) tests for prevention and early detection, alongside exploring the associated barriers to these tests. A stratified national survey was conducted in Chile, involving 1893 respondents (with a 2.3% error margin and 95% confidence interval). Logistic and multinomial regression analyses were employed to examine variations in test utilization likelihood and barrier. We found that the key determinants for undergoing CRC tests included age, health status, possession of private health insurance, and attainment of postgraduate education. Notably, 18% and 29% of respondents covered by public and private insurance, respectively, cited personal prevention as the primary motivation for test uptake. The principal obstacle identified was lack of knowledge, mentioned by 65% of respondents, while 29% and 19% of the publicly and privately insured respectively highlighted lack of access as a barrier. The results of this study provide valuable insights into factors influencing CRC screening, aiming to inform public health policies for expanding national coverage beyond diagnosis and treatment to encompass preventive measures.

Colorectal cancer initiation: Understanding early-stage disease for intervention.

How tumors arise or the cause of precancerous lesions is a fundamental question in cancer biology. It is generally accepted that tumors originate from normal cells that undergo uncontrolled proliferation owing to genetic alterations. At the onset of adenoma formation, cancer driver mutations confer clonal growth advantage, enabling mutant cells to outcompete and eliminate the surrounding healthy cells. Hence, the development of precancerous lesions is not only attributed to the expansion of pre-malignant clones, but also relies on the relative fitness of mutated cells compared to the neighboring cells. Colorectal cancer (CRC) is an excellent model to investigate cancer origin as it follows a stereotypical process from mutant cell hyperplasia to adenoma formation and progression. Here, we review the evolving understanding of colonic tumor development, focusing on how cell intrinsic and extrinsic factors impact cell competition and the "clone war" between cancer-initiating cells and normal stem cells. We also discuss the promises and limitations of targeting cell competitiveness in cancer prevention and early intervention. The field of tumor initiation is currently in its infancy, elucidating the adenoma origin is crucial for designing effective prevention strategies and early treatments before cancer becomes incurable.

Screening for Colorectal Cancer.

Colorectal cancer (CRC) is the second leading cause of cancer death. Screening has been proven to reduce both cancer incidence and cancer-related mortality. Various screening tests are available, each with their own advantages and disadvantages and varying levels of evidence to support their use. Clinicians should offer CRC screening to average-risk persons aged 50 to 75 years; starting screening at age 45 years remains controversial. Screening may be beneficial in select persons aged 76 to 85 years, based on their overall health and screening history. Offering a choice of screening tests or sequentially offering an alternate test for those who do not complete screening can significantly increase participation.

Engaging with Rural Communities for Colorectal Cancer Screening Outreach Using Modified Boot Camp Translation.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality are disproportionately high among rural residents and Medicaid enrollees. OBJECTIVES: To address disparities, we used a modified community engagement approach, Boot Camp Translation (BCT). Research partners, an advisory board, and the rural community informed messaging about CRC outreach and a mailed fecal immunochemical test program. METHODS: Eligible rural patients (English-speaking and ages 50-74) and clinic staff involved in patient outreach participated in a BCT conducted virtually over two months. We applied qualitative analysis to BCT transcripts and field notes. RESULTS: Key themes included: the importance of directly communicating about the seriousness of cancer, leveraging close clinic-patient relationships, and communicating the test safety, ease, and low cost. CONCLUSIONS: Using a modified version of BCT delivered in a virtual format, we were able to successfully capture community input to adapt a CRC outreach program for use in rural settings. Program materials will be tested during a pragmatic trial to address rural CRC screening disparities.

The future of cancer vaccines against colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is the second most lethal malignancy worldwide. Immune checkpoint inhibitors (ICIs) benefit only 15% of patients with mismatch repair-deficient/microsatellite instability (dMMR/MSI) CRC. The majority of patients are not suitable due to insufficient immune infiltration. Cancer vaccines are a potential approach for inducing tumor-specific immunity within the solid tumor microenvironment. AREA COVERED: In this review, we have provided an overview of the current progress in CRC vaccines over the past three years and briefly depict promising directions for further exploration. EXPERT OPINION: Cancer vaccines are certainly a promising field for the antitumor treatment against CRC. Compared to monotherapy, cancer vaccines are more appropriate as adjuvants to standard treatment, especially in combination with ICI blockade, for microsatellite stable patients. Improved vaccine construction requires neoantigens with sufficient immunogenicity, satisfactory HLA-binding affinity, and an ideal delivery platform with perfect lymph node retention and minimal off-target effects. Prophylactic vaccines that potentially prevent CRC carcinogenesis are also worth investigating. The exploration of appropriate biomarkers for cancer vaccines may benefit prognostic prediction analysis and therapeutic response prediction in patients with CRC. Although many challenges remain, CRC vaccines represent an exciting area of research that may become an effective addition to current guidelines.

Consumption of Feed Supplemented with Oat Beta-Glucan as a Chemopreventive Agent against Colon Cancerogenesis in Rats.

Colorectal cancer (CRC) accounts for 30% of all cancer cases worldwide and is the second leading cause of cancer-related deaths. CRC develops over a long period of time, and in the early stages, pathological changes can be mitigated through nutritional interventions using bioactive plant compounds. Our study aims to determine the effect of highly purified oat beta-glucan on an animal CRC model. The study was performed on forty-five male Sprague-Dawley rats with azoxymethane-induced early-stage CRC, which consumed feed containing 1% or 3% low molar mass oat beta-glucan (OBG) for 8 weeks. In the large intestine, morphological changes, CRC signaling pathway genes (RT-PCR), and proteins (Western blot, immunohistochemistry) expression were analyzed. Whole blood hematology and blood redox status were also performed. Results indicated that the histologically confirmed CRC condition led to a downregulation of the WNT/ß-catenin pathway, along with alterations in oncogenic and tumor suppressor gene expression. However, OBG significantly modulated these effects, with the 3% OBG showing a more pronounced impact. Furthermore, CRC rats exhibited elevated levels of oxidative stress and antioxidant enzyme activity in the blood, along with decreased white blood cell and lymphocyte counts. Consumption of OBG at any dose normalized these parameters. The minimal effect of OBG in the physiological intestine and the high activity in the pathological condition suggest that OBG is both safe and effective in early-stage CRC.

Antitumor Effect and Gut Microbiota Modulation by Quercetin, Luteolin, and Xanthohumol in a Rat Model for Colorectal Cancer Prevention.

Colorectal cancer stands as the third most prevalent form of cancer worldwide, with a notable increase in incidence in Western countries, mainly attributable to unhealthy dietary habits and other factors, such as smoking or reduced physical activity. Greater consumption of vegetables and fruits has been associated with a lower incidence of colorectal cancer, which is attributed to their high content of fiber and bioactive compounds, such as flavonoids. In this study, we have tested the flavonoids quercetin, luteolin, and xanthohumol as potential antitumor agents in an animal model of colorectal cancer induced by azoxymethane and dodecyl sodium sulphate. Forty rats were divided into four cohorts: Cohort 1 (control cohort), Cohort 2 (quercetin cohort), Cohort 3 (luteolin cohort), and Cohort 4 (xanthohumol cohort). These flavonoids were administered intraperitoneally to evaluate their antitumor potential as pharmaceutical agents. At the end of the experiment, after euthanasia, different physical parameters and the intestinal microbiota populations were analyzed. Luteolin was effective in significantly reducing the number of tumors compared to the control cohort. Furthermore, the main significant differences at the microbiota level were observed between the control cohort and the cohort treated with luteolin, which experienced a significant reduction in the abundance of genera associated with disease or inflammatory conditions, such as Clostridia UCG-014 or Turicibacter. On the other hand, genera associated with a healthy state, such as Muribaculum, showed a significant increase in the luteolin cohort. These results underline the anti-colorectal cancer potential of luteolin, manifested through a modulation of the intestinal microbiota and a reduction in the number of tumors.

Study protocol for a mixed methods approach to optimize colorectal cancer screening in Malaysia: Integrating stakeholders insights and knowledge-to-action framework.

INTRODUCTION: Colorectal cancer is a growing global health concern and the number of reported cases has increased over the years. Early detection through screening is critical to improve outcomes for patients with colorectal cancer. In Malaysia, there is an urgent need to optimize the colorectal cancer screening program as uptake is limited by multiple challenges. This study aims to systematically identify and address gaps in screening service delivery to optimize the Malaysian colorectal cancer screening program. METHODS: This study uses a mixed methods design. It focuses primarily on qualitative data to understand processes and strategies and to identify specific areas that can be improved through stakeholder engagement in the screening program. Quantitative data play a dual role in supporting the selection of participants for the qualitative study based on program monitoring data and assessing inequalities in screening and program implementation in healthcare facilities in Malaysia. Meanwhile, literature review identifies existing strategies to improve colorectal cancer screening. Additionally, the knowledge-to-action framework is integrated to ensure that the research findings lead to practical improvements to the colorectal cancer screening program. DISCUSSION: Through this complex mix of qualitative and quantitative methods, this study will explore the complex interplay of population- and systems-level factors that influence screening rates. It involves identifying barriers to effective colorectal cancer screening in Malaysia, comparing current strategies with international best practices, and providing evidence-based recommendations to improve the local screening program.

The implementation and mechanisms of advance notification for cancer screening: A scoping review.

OBJECTIVE: To describe and synthesise information on the content and delivery of advance notifications (information about cancer screening delivered prior to invitation) used to increase cancer screening participation and to understand the mechanisms that may underlie their effectiveness. METHODS: Searches related to advance notification and cancer screening were conducted in six electronic databases (APA PsycINFO, CINAHL, Cochrane Library, Embase, PubMed, Web of Science) and results were screened for eligibility. Study characteristics, features of the advance notifications (cancer type, format, delivery time, and content), and the effect of the notifications on cancer screening participation were extracted. Features were summarised and compared across effective versus ineffective notifications. RESULTS: Thirty-two articles were included in this review, reporting on 33 unique advance notifications. Of these, 79% were sent via postal mail, 79% were distributed prior to bowel cancer screening, and most were sent 2 weeks before the screening offer. Twenty-two full versions of the advance notifications were obtained for content analysis. Notifications included information about cancer risk, the benefits of screening, barriers to participation, social endorsement of cancer screening, and what to expect throughout the screening process. Of the 19 notifications whose effect was tested statistically, 68% were found to increase screening (by 0.7%-16%). Effectiveness did not differ according to the format, delivery time, or content within the notification, although some differences in cancer type were observed. CONCLUSION: Future research should explore the effectiveness of advance notification via alternative formats and for other screening contexts and disentangle the intervention- and person-level factors driving its effect on screening participation.

Community Health workers United to Reduce Colorectal cancer and cardiovascular disease among people at Higher risk (CHURCH): study protocol for a randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is the second most lethal cancer in the United States (U.S.) with the highest incidence and mortality rates among African Americans (AAs) compared to other racial groups. Despite these disparities, AAs are the least likely to undergo CRC screening, have precancerous colorectal polyps removed, and have CRC detected at stages early enough for curative excision. In addition, compelling evidence links inflammatory dietary patterns to increased CRC and cardiovascular disease risk. Studies show that AA churches can successfully engage in health promotion activities including those related to cancer control. The current study seeks to leverage church-placed Community Health Workers (CHWs) to increase CRC screening and reduce CRC risk. DESIGN AND METHODS: We aim to (1) increase guideline concordant CRC screening uptake using church-placed CHWs trained in screening with a validated instrument, Brief Intervention using Motivational Interviewing, and Referral to Treatment (SBIRT); and (2) reduce dietary risk factors (inflammatory dietary patterns) linked to CRC. The latter will be addressed by culturally adapting an existing, web-based lifestyle program called Alive!. Using a Hybrid Type 1 Implementation-Effectiveness cluster randomized design, we will randomize 22 AA churches into either the dual intervention arm (CHW-led SBIRT intervention plus Alive!) or a usual care arm comprised of CRC prevention educational pamphlets and a list of CRC screening sites. We will recruit 440 subjects and evaluate the effects of both arms on screening uptake (colonoscopy, fecal DNA) (primary outcome) and dietary inflammation score (secondary outcome) at 6-month follow-up, and Life Simple7 (LS7)-a cardiovascular disease (CVD) risk score-at 6 months and 1 year (secondary outcome). Finally, guided by a racism-conscious adaptation of the Consolidated Framework for Implementation Research (CFIR), we will conduct a mixed-methods process evaluation with key stakeholders to understand multi-level influences on CRC screening and CVD risk behaviors. DISCUSSION: Church-placed CHWs are trusted influential connectors between communities and health systems. Studies have shown that these CHWs can successfully implement health prevention protocols in churches, including those related to cancer control, making them potentially important community mediators of CRC screening uptake and CRC/CVD risk reduction. TRIAL REGISTRATION: NCT05174286; clinicaltrials.gov; August 31st, 2023.

Evaluation of the "Burgenland PREvention trial of colorectal cancer Disease with ImmunologiCal Testing" (B-PREDICT)-a population-based colorectal cancer screening program.

BACKGROUND: The colorectal cancer (CRC) screening program B-PREDICT is a population based invited two stage screening project using a faecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. B-PREDICT was compared with the opportunistic screening colonoscopy (OPP-COL), performed in course of the nationwide screening program. METHODS: Within B-PREDICT all residents of the Austrian federal state Burgenland, aged between 40 and 80 are annually invited to FIT testing. All individuals who underwent initial colonoscopy in Burgenland between 01/2003 and 12/2014, were included in this study. Individuals from the FIT-triggered invited screening program B-PREDICT were compared with those from the non-FIT triggered OPP-COL. RESULTS: 15 133 individuals from B-PREDICT were compared to 10 045 individuals with OPP-COL. CRC detection rates were 1.34% (CI-95%, [1.15; 1.52]) in B-PREDICT compared to 0.54% in OPP-COL (95%-CI, [0.39; 0.68] p < 0.001). The decrease in the age standardized incidence rates of CRC was more pronounced in the population screened with FIT than in the general population screened with colonoscopy. Changes in incidence rates per year were -4.4% (95%-CI, [-5.1; -3.7]) vs. -1.8% (95%-CI, [-1.9; -1.6] p < 0.001). CONCLUSIONS: B-PREDICT shows a two-fold higher detection rate of CRC as well as HRA compared to OPP-COL.