CRC Risk Research Articles

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

BackgroundColorectal 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 methodsWe 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.DiscussionChurch-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 registrationNCT05174286; clinicaltrials.gov; August 31st, 2023

Abstract LB375: Multimodality dietary intervention for colorectal cancer prevention: The MyBestGI randomized trial

Abstract Colorectal cancer (CRC) is one of the cancers most highly affected by diet. Recommendations for reducing risk of CRC include weight management, eating plentiful plant-based high fiber foods, and limiting intakes of red meats and ultra-processed foods. In addition, an increased proportion of monounsaturated and omega-3 fats in the diet is beneficial for promoting weight management and reducing inflammation. Despite the evidence supporting the importance of diet and the demonstrated success for eliciting dietary changes in research settings, simple methods that can be easily implemented in medical settings are lacking. We developed a bespoke mHealth app (MyBestGI), incorporating an autonomy-supporting, self-regulatory approach to behavior change. The program promotes identification of the benefits of healthy eating on well-being. Two versions of the program are being tested in a 12-month, 3-arm randomized trial that seeks to recruit 240 people at increased risk for CRC. Participants are randomized to either 1) a control group that receives written information on cancer preventive diets, 2) a treatment group that receives a MyBestGI app version for logging 4 food groups associated with increased risks of CRC (red meats, processed meats, added sugars and refined grains), or 3) a treatment group that receives a MyBestGI app version for logging the same 4 food groups to limit plus 7 food groups to encourage in personalized quantities. The two treatment groups also receive a user manual, behavior-oriented, biweekly text messages, and supportive coaching calls. Logging food groups is requested at least 3 per week for 3 months, and 3 per week every other week for the next 9 months. The app displays logging results relative to individualized targets and has features that prompt reflecting on the user’s own results and planning for future eating. The primary endpoints are weight loss and improvement in a dietary cancer prevention score. Recruitment began in June 2023, and the study is enrolling 8-10 participants per month. The drop-out rate is lower than expected. Compliance with study procedures and app use is high. Responses to the end-of-day reflection questions within the app show that 92% of users are neutral, happy, or very happy with their dietary behavior for the day. For the 15 participants who had 12 weeks of logging data available, foods were logged for an average of 38 days (range 20-75) which is slightly higher than the requested logging of 36 days over 12 weeks. Review of the support calls for protocol fidelity indicates participants are enthusiastic about the MyBestGI program, making changes in their eating, and are internalizing the autonomy-supporting beliefs promoted in the program. These early results suggest users are engaging with the MyBestGI app at a very high level, making use of the provided app features, and enjoying the program. The MyBestGI approach therefore has excellent potential to support dietary change towards a cancer preventive diet in a format that is facile to implement in high-risk populations. Citation Format: Zora Djuric, Michelle Segar, Ananda Sen, Reema Kadri, Rob Adwere-Boamah, Juno Orr, Katherine Poore, Samara Rifkin, Lorraine Buis. Multimodality dietary intervention for colorectal cancer prevention: The MyBestGI randomized trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB375.

Insights Into Colorectal Cancer Screening: A Multidatabase Cohort Study of Over 1.5 Million Taiwanese

IntroductionColorectal cancer (CRC) remains a significant public health concern. This study aims to provide a comprehensive understanding of the effectiveness of fecal immunochemical test (FIT) screening on CRC incidence and mortality, leveraging the scale of over 1.5 million randomly selected Taiwanese participants and more than 11.7 million person-years of follow-up. MethodsThis prospective cohort study merges data from three robust Taiwanese health databases: the CRC screening program, cancer registration, and death registration databases. Incidence and mortality rates of CRC were calculated based on age, sex, urbanization, and past screening status. Cox proportional hazard models were used to assess the association between screening statuses and CRC incidence or mortality, adjusting for age, sex, and urbanization levels. Statistical analysis of the data was conducted in 2021-2022. ResultsFIT screening was associated with a 33% reduction in CRC incidence and a 47% reduction in mortality. The study identified a dose-response relationship between the fecal hemoglobin concentration (f-HbC) levels and CRC risk. Participants with consistent FIT-negative results had significantly reduced CRC incidence and mortality risks, while those with one or more positive FIT results faced increased risks. Notably, compliance with follow-up examinations after a positive FIT significantly lowered mortality risk. ConclusionsThis large-scale study validates the efficacy of FIT screening in reducing CRC incidence and mortality. It offers a nuanced understanding of how various screening statuses impact CRC risks, thus providing valuable insights for public health strategies aimed at CRC prevention.

Variable role of diet-related risk factors for colorectal cancer – A cross-sectional analysis of regional differences

Background and objectives. Diet is the crucial environmental factor in sporadic colorectal cancer. Its complexity and diversity reflect our cultural and historical background, and could potentially explain why the existing public health strategies focused on colorectal cancer are failing. Materials and methods. An observational cross-sectional study encompassed 60 non-metastatic CRC patients to assess dietary factors related to colorectal cancer, with regard to their traditional diet i.e. the region they come from. Patients were recruited from two regions (30 patients per region), in one (Slavonia) traditional diet is abundant in well-known dietary risk factors for colorectal cancer, and in the second (Dalmatia) traditional diet is the Mediterranean type. Results. Based on the logistic regression analysis, patients from Dalmatia have a 24% higher risk for the high-risk diet in comparison to patients from Slavonia (OR = 1.240, 95% CI 1.195 – 9.990, P=0.022). Identified independent risk factors include weight loss in the last 3 months along with daily alcohol consumption which were found to increase CRC risk by 61.4% and 53.1%, respectively. Conclusions. Our results support statistical data showing that colorectal cancer incidence is higher in the Mediterranean region, suggesting a shift in the Mediterranean dietary pattern, which in our case were higher obesity rates, daily alcohol consumption and abundance of unfavorable dietary habits.

Abstract 7324: Impact of BMI on immune pathways in preinvasive colorectal lesions

Abstract Background: Obesity is a risk factor for colorectal neoplasia, possibly mediated by metabolic dysregulation or chronic inflammation. Circulating inflammatory cytokines have been associated with an increased risk of CRC, but no studies have examined the impact of BMI on immune gene expression in preinvasive lesions. Our analysis combines data from 3 retrospective epidemiologic studies among patients with colorectal adenomas or serrated polyps. Using a cross-sectional design, we investigate whether BMI categories (obese (OB), overweight (OW), normal (NL)) are associated with T-helper gene pathways. Methods: For each patient, we include demographic, clinical, and specimen (archival FFPE for RNA isolation) data. Immune gene expression data was determined using the NanoString nCounter platform on a subset of cases (n=100) balanced by study site and lesion type from our cohort (n=630). Genes were normalized using a modified RUVseq methodology. We examined 4 pathways (Th1, Th2, Th17, Treg) defined by gene lists included in the NS immune v2. panel. Differences in pathway expression by BMI categories were analyzed using our distance-based methods (Wd* multivariate analysis of variance and TW2 pairwise method) adjusted for age & sex. Using linear regression analysis, we generated coefficients (p-values) for OW and OB vs NL for genes within each pathway. Results: 86 samples passed QC. Th2 and Th1 pathways were significant for OW vs NL (p<0.05) whereas Th17 was marginally significant (<0.1). Several genes within the Th1, Th2, and Th17 pathways were enriched in OW vs. NL: e.g., IL2 (coeff. 0.77 (p=0.008), IL5 (coeff. 1.02, p=0.001), IL17F (coeff. 0.57, p=0.05), respectively. (Table) Conclusion: Enrichment of genes specific to the Th pathways in OW persons suggest that metabolic immune modulation may be important in early colorectal carcinogenesis. Differences in immune pathway and gene expression by BMI categories TW2 (p-value) Wd* (p-value) Pathways Normal (N = 22) Overweight (N = 32) Obese (N = 29) Th2 Ref. 0.017 0.15 0.038 Th1 Ref. 0.03 0.204 0.10 Th17 Ref. 0.073 0.125 0.103 MLR coefficient (p-value) Pathway Gene Overweight vs. Normal Obese vs. Normal ANOVA (p-value) Th2 IL2RA 0.34 (0.041) -0.11 (0.517) 0.010 IL4 0.58 (0.019) 0.22 (0.386) 0.052 IL5 1.02 (0.001) 0.41 (0.191) 0.004 NOTCH1 -0.05 (0.742) -0.34 (0.045) 0.078 Th1 IL12B 0.57 (0.031) 0.40 (0.136) 0.093 IL2 0.77 (0.008) 0.39 (0.179) 0.028 TBX21 0.46 (0.015) 0.19 (0.308) 0.044 Th17 IL17F 0.57 (0.050) 0.42 (0.157) 0.139 IL21 0.77 (0.004) 0.42 (0.131) 0.017 IL23R 0.29 (0.048) -0.008 (0.957) 0.047 IL6R 0.002 (0.990) 0.36 (0.039) 0.041 IRF4 -0.61 (0.007) -0.33 (0.149) 0.025 TGFB1 -0.26 (0.023) -0.19 (0.101) 0.069 Citation Format: Lauren R. Fanning, Bashir Hamidi, Ivan Korostenskij, Souvik Seal, Tami L. Crawford, Todd A. MacKenzie, Elizabeth L. Barry, Jessica E. Thaxton, Martha J. Shrubsole, Benjamin Vincent, John A. Baron, Alexander V. Alekseyenko, Kristin Wallace. Impact of BMI on immune pathways in preinvasive colorectal lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7324.

Selenium levels in colorectal cancer: A systematic review and meta-analysis of serum, plasma, and colorectal specimens

BackgroundColorectal cancer (CRC) is a growing public health problem. Several clinical studies have shown a potentially protective effect of selenium (Se), but the reports are inconsistent. The objective of the study was to examine the evidence for relation between serum/tissue Se status and CRC. Method and materialsIn this Systematic Review and Meta-Analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum/plasma/whole blood/tissue Se concentrations in CRC patients and controls for articles published till August 2023. Meta-analysis was performed, and study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary mean differences in serum levels of Se between CRC patients and healthy controls, and Se levels between malignant and matched non-malignant tissue specimens were assessed. ResultsAfter initial screening, a total of 24 studies (18 serum and 6 tissue studies) with a pooled total of 2640 participants were included in the meta-analysis. CRC patients had significantly lower serum Se levels than healthy controls, being the difference between the two equal to 3.73 µg/dl (95% CI: 6.85–0.61). However, the heterogeneity was very high, I2= 99% (p < 0.01). Our meta-analysis showed higher Se levels in CRC cancerous specimens than in matched healthy colon tissue: the increase was equal to 0.07 µg/g wet tissue weight (95% CI: 0.06–0.09; p= 0.02). ConclusionsCRC patients have lower serum and higher colon cancerous tissue Se levels. Some factors, such as Se levels in different tumor grades of CRC need to be further considered for a more conclusive association between Se levels and risk of CRC.

Artificially sweetened beverages consumption and risk of obesity-related cancers: a wide-angled Mendelian randomization study.

The impact of artificially sweetened beverages (ASBs) consumption on obesity-related cancers (ORCs) risk remains controversial. To address this challenging issue, this study employed wide-angle mendelian randomization (MR) analyses to explore the genetic causality between ASB consumption and the risk of ORCs, thereby effectively minimizing the impact of external confounders. We conducted a suite of analyses encompassing univariable, multivariable, and two-step MR to evaluate causal associations between ASB consumption (samples = 85,852) and risk of ORCs (total samples = 2,974,770) using summary statistics from genome-wide association studies (GWAS). Total, direct, and intermediary effects were derived by performing inverse-variance weighted (IVW), MR-Egger, weighted mode, weighted median, and lasso method. Additionally, we performed an extensive range of sensitivity analyses to counteract the potential effects of confounders, heterogeneity, and pleiotropy, enhancing the robustness and reliability of the findings. Genetically predicted ASB consumption was positively associated with the risk of colorectal cancer (CRC, p = 0.011; OR: 6.879; 95% CI: 1.551, 30.512 by IVW) and breast cancer (p = 0.022; OR: 3.881; 95% CI: 2.023, 9.776 by IVW). Multivariable analysis yielded similar results. The results of the two-step MR unveiled that body mass index (BMI) assumes a pivotal role in mediating the association between ASB consumption and CRC risk (intermediary effect = 0.068, p = 0.024). No causal connection exists between ASB consumption and the majority of ORCs, in addition to CRC and breast cancer. Additionally, our findings suggest that BMI might be a potential mediator in the association between ASB consumption and CRC.

Inappropriate Ordering of Multitarget Stool DNA Tests for Colon Cancer Screening.

CRC screening is recommended for adults aged 45-75. Mt-sDNA is indicated for asymptomatic individuals between the ages of 45 and 85, but not for those with rectal bleeding, iron deficiency anemia, adenomatous polyps, previous colonoscopy within 10 years, family history of CRC, positive results from CRC screening tests within the past 6 months, or age less than 45 and greater than 85. We aimed to determine the prevalence of mt-sDNA use when not indicated and factors associated with inappropriate testing. 7,345 patients underwent mt-sDNA testing and were randomized using EMERSE. Charts for the first 500 patients were reviewed to determine whether mt-sDNA was ordered appropriately according to the USPSTF criteria. Seven patients were excluded due to having more than one inappropriate ordering for mt-sDNA. Of 500 patients, 22.2% had an inappropriately ordered mt-sDNA test. The most common reason for inappropriate ordering was having a previous colonoscopy done within the past 10 years. Rates of inappropriate testing significantly varied by race and the specialty of the ordering provider, with internal medicine providers ordering the most mt-sDNA tests. Rates of inappropriate testing did not significantly vary by sex or type of insurance. Our study suggests that providers may not be familiar with guidelines for the indicated use of mtsDNA, leading to inappropriate referrals and increased costs. Patients at increased CRC risk would benefit from a more sensitive procedure such as a colonoscopy. Future studies could understand the motivation to order testing outside approved indications through provider surveys and interviews.

Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis.

Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10-3). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.

The effect of air pollution on the risk of inflammatory bowel disease, colorectal cancer and appendicitis

Introduction and objective&#x0D; Intense industrial development is contributing to increased emissions of air pollutants. Numerous studies indicate a link between air pollution and a higher risk of pulmonary and cardiovascular diseases. Our goal is to analyze available scientific studies to demonstrate the relationship between air pollution and the risk of developing and complicating inflammatory bowel disease, colorectal cancer and appendicitis.&#x0D; Brief description of the state of knowledge&#x0D; Air pollution is a global health challenge. Particles such as PM, nitrogen oxides, sulfur oxides or ozone have a significant impact on health. Studies suggest a link between pollution and intestinal diseases (IBD, CRC, appendicitis). Air pollutants can affect the gut by causing inflammation, oxidative stress and disruption of the gut microbiota. Exposure to PM2.5 can increase the risk of IBD, CRC, and PM10 can increase the risk of UC. There is a correlation between pollution and the rate of hospitalization for IBD. In addition, exposure to PM2.5 increases the risk of colorectal cancer mortality. Short-term exposure to air pollution is associated with more hospitalizations for appendicitis.&#x0D; Summary&#x0D; Air pollution is a real health risk. Reducing air pollution could potentially reduce the risk of developing these intestinal diseases and their complications. Despite the potential links, further research is required to better understand the mechanisms of action of pollutants on intestinal health. Urgent and coordinated global and local action is needed to reduce air pollution emissions and protect the health of the public.

A145 UNDERWATER EMR FOR LARGE FLAT DYSPLASTIC COLORECTAL LESIONS IN PATIENTS WITH CHRONIC ULCERATIVE COLITIS

Abstract Background Patients with chronic ulcerative colitis are at increased risk of colorectal cancer, in part due to increased prevalence of dysplastic lesions. To reduce CRC risk, endoscopic resection is preferable to surgery if feasible. However, large flat lesions can be challenging to remove endoscopically. We report our experience with underwater EMR for large, flat ulcerative colitis-associated dysplastic lesions. Aims To evaluate the safety and efficacy of UEMR for treatment of flat/sessile colorectal lesions with dysplasia, without overt signs of invasive cancer. To analyze rates of complications and outcomes for patients undergoing UEMR and compare to alternative methods of treatment for similar lesions. Methods We reviewed our IBD patient database from 2021 to 2023 for ulcerative colitis patients referred for large (≥ 20 mm diameter) flat/sessile colorectal lesions without overt signs of invasive cancer, who subsequently underwent underwater EMR. The procedure was performed by an endoscopist with extensive experience in UEMR for large colorectal lesions. Results Eleven de novo lesions in 8 patients (4 female; age 58 ± 14) were successfully treated with single-session UEMR. Mean lesion size was 42 ± 22 mm (range 20 to 80 mm); all morphologically flat (Paris IIa or IIb). Three cases were resected en bloc; the remainder piecemeal. Pathology showed tubulovillous adenoma, N=4 (36%); tubular adenoma, N=5 (45%); traditional serrated adenoma, N=1 (9%); sessile serrated lesion, N=1, (9%); high-grade dysplasia, N=1 (9%). There were no cases of invasive cancer. Endoscopic follow-up available for 5 patients over 10.4 ± 2 months showed benign diminutive recurrent/residual lesions in 2 cases, both amenable to UEMR. There were no procedural complications. Conclusions In this series of large, flat dysplastic CUC-associated lesions, UEMR was safe and effective, obviating surgery and endoscopic submucosal dissection. Funding Agencies None

P665 Statins use and the risk of colorectal cancer in patients with inflammatory bowel disease: A Systematic review and meta-analysis

Abstract Background Statin use has been linked to a reduced risk of advanced colorectal adenomas; however, its association with colitis-associated dysplasia and cancer is not well-defined. We aimed to perform a systematic review and meta-analysis to assess the pooled association of statin exposure with dysplasia and colorectal cancer in patients with inflammatory bowel disease (IBD). Methods We searched MEDLINE, EMBASE, and the COCHRANE library to identify full text articles analyzing the risk of CRC or dysplasia development based on statin use in patients with IBD. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs] or odds ratios [ORs], following the data format specified in the individual studies. Results A total of 4 studies were identified as eligible for the meta-analysis. In the analysis of studies presented with time-to-event outcomes, statin use was associated with a statistically significant reduction in risk of colorectal cancer (HR 0.76, 95% confidence interval [CI] 0.61-0.95, P=0.016). Meanwhile, in the analysis of non-time-to-event study results, statin use was associated with a trend towards lower colorectal cancer risk (OR 0.28, 95% CI 0.07-1.10, P=0.068). Conclusion Statin use appears to be associated with a reduced risk of colorectal cancer in patients with inflammatory bowel disease. Statins may serve as potential chemopreventive agents for long-standing IBD patients, and further large-scale prospective studies will be needed to confirm its potential benefit.

Association of Methylenetetrahydrofolate Reductase rs1801133 Gene Polymorphism with Cancer Risk and Septin 9 Methylation in Patients with Colorectal Cancer

PurposeColorectal cancer (CRC) is one of the most common malignancies, with a high incidence and mortality worldwide. Methylated Septin 9 (mSEPT9) has been used clinically as an auxiliary tool for CRC screening. The aim of the present study was to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism with the risk of CRC and the methylation status of Septin 9 in CRC.MethodsInformation of 540 patients with a confirmed diagnosis of CRC and with a physical examination were utilized to assess the association of the MTHFR rs1801133 polymorphism with CRC and the methylation of SEPT9. MTHFR rs1801133 polymorphism was genotyped using polymerase chain reaction (PCR). The commercial Septin 9 Gene Methylation(mSEPT9) Detection Kit was used for plasma SEPT9 methylation analysis.ResultsAmong 540 patients, 61.48% were men and the median age was 54.47 ± 13.14. 65.37% of all colorectal tumors developed in the rectum. 195 patients had negative mSEPT9 methylation, while 345 had positive results. 87 individuals with stage I, 90 with stage II, 287 with stage III, and 76 with stage IV colorectal cancer were included in the sample. The results demonstrated that the positivity rate and degree of methylation of mSEPT9 were remarkably higher in patients with more advanced TNM stages than in those with less advanced stages. The frequencies of the MTHFR rs1801133 CC genotype and allele C carriers in patients with CRC were significantly higher than those in healthy individuals (P = 0.006 and P = 0.001, respectively). The positivity rate of the mSEPT9 assay was significantly higher among the MTHFR rs1801133 TT genotype and allele T carriers than among the CC and allele C carriers respectively. The MTHFR rs1801133 TT genotype and allele T carriers were positively associated with the methylation of SEPT9 (OR = 3.320, 95% CI 1.485–7.424, P = 0.003 and OR = 1.783, 95% CI 1.056–3.010, P = 0.030, respectively).ConclusionIn conclusion, individuals harboring the MTHFR rs1801133 CC genotype had a higher risk of CRC and the MTHFR rs1801133 TT carriers were more susceptible to Septin 9 gene methylation.

Multisite external validation of blood test for colorectal neoplasia screening in a majority average-risk screening cohort of 449 subjects.

66 Background: The FirstSight CRC screening blood test was previously shown to have sensitivities of 92.1% and 54.5% for CRC and AA at a specificity of 90.6% for 1,038 subjects from 18 clinical sites. In this report, we describe the independent external validation of the predefined FirstSight CRC screening blood test with new subjects from 16 sites dispersed across the US, 4 of which are new and did not participate in the previous study. Methods: The validation study included subjects from two sources: Average-risk, asymptomatic screening subjects from screening clinics supplemented with diseased-only subjects from surgical oncology centers. Blood was drawn before bowel prep for colonoscopy or treatment. External validation as well as Monte Carlo cross-validation (MCCV) methods were used to evaluate the performance of the pre-defined FirstSight assay, algorithm, and clinical thresholds in this independent external validation set. Results include sensitivity and specificity to detect CRC and AA and 95% confidence intervals. Results: The study cohort (55.2% female; mean age 56.9 yrs.) consisted of 449 subjects (White 61.7%; Black 14.5%; Hispanic 18%; AAPI and Middle Easterners 5.8%). The majority of them, 376 (84%), were asymptomatic, average-risk screening subjects (including 1 CRC, 53 AA, and all 322 negative subjects). An additional 73 (16%) diseased subjects (39 CRC and 34 AA) were enriched due to low disease prevalence. The FirstSight algorithm derives a test score from 0 to 100 as a quantitative measure of AA and CRC risk with a cutpoint to assign a binary low- or high-risk designation. The previously described cutpoint of 47.2 yielded a test specificity of 90.0%, and 90.0% and 52.9% sensitivity for the detection of CRC and AA, respectively. Here we report a higher cutpoint 50 with identical sensitivities but improved specificity to 90.7%. Point estimates of sensitivity and specificity, including CRC staging, and Clopper-Pearson exact 95% confidence intervals based on the external validation results are presented below. Conclusions: An external validation included 449 subjects from a multi-site, majority average-risk CRC screening study successfully validated the FirstSight Blood Test’s high performance as previously established with 1,038 subjects. The results bring forth confidence in the Test’s reproducibility in a large-scale clinical trial. Clinical trial information: NCT05127096 . [Table: see text]

Colorectal Cancer Alliance: Promoting prevention and early detection with screening navigation and a personalized recommendation via a digital screening quiz tool for colorectal cancer.

71 Background: Evaluating the effectiveness of a Colorectal Cancer screening navigation model delivered in a digital platform offered by a patient advocacy organization. Designed as a digital screening quiz tool and live navigation to promote CRC screening, the Colorectal Cancer Alliance’s Screening Quiz is a risk stratification tool that connects respondents to live certified cancer care navigators delivering evidence-based interventions to increase CRC screening, education and patient and family support. The framework utilizes small and mass media, one-on-one education and patient navigation services to help address and reduce barriers to care. Critical interventions which research shows that on-time screening for CRC leads to better outcomes. Methods: The Screening Quiz has been promoted through social sharing, community outreach, media, including influencer campaigns to increase outreach to at-risk communities. Questions assess personal and family history, hereditary syndromes, and demographics to provide a CRC screening recommendation based on current USPSTF guidelines. Respondents overdue for screening who opt in, are triaged to the Alliance’s patient navigation team for follow-up. This interaction includes phone calls and emails for symptomatic individuals or at high risk for CRC, telephonic and email for average-risk uninsured, and emails for average-risk insured. At-risk individuals are connected to resources, such as financial assistance, free at-home screening tests, and colonoscopy scheduling services. Results: July 2022 to August 2023, the Screening Quiz provided over 30,000 screening recommendations. The median age of respondents was 48; 33% of the respondents were between the ages of 45 to 64. Of the respondents, 29% were male and 71% were female. Most were White (74.3%), but nearly half of those who opted into navigation identified as BIPOC, including 14.4% Black/AA, 17.8% Hispanic or Latino, 7.7% Asian, and 2.5% AI/AN. Most respondents were symptomatic (65.5%) but 7.3% were asymptomatic high-risk. These two groups represented 88% of 1,851 respondents triaged to patient navigation. Conclusions: This digital screening tool and live navigation framework may serve as a key solution in driving CRC screening compared to other interventions. Providing access to live navigation, educational resources, and support services for CRC screening and diagnosis.The Alliance is uniquely positioned with its national network of volunteers, partners, and community presence to effectively reach at-risk communities. Aligning with the science of evidence-based interventions, the Alliance will continue to leverage the Screening Quiz in partnership with healthcare and community stakeholders to close Colorectal Cancer screening gaps.

Impact of AI-aided colonoscopy in clinical practice: a prospective randomised controlled trial

ObjectiveColorectal cancer (CRC) has a significant role in cancer-related mortality. Colonoscopy, combined with adenoma removal, has proven effective in reducing CRC incidence. However, suboptimal colonoscopy quality often leads to missed...

A nudge strategy to increase the uptake of colorectal cancer screening in Saudi Arabia: A pragmatic randomized trial in the Hail region.

The purpose of this research was to examine the effectiveness of using a nudge strategy to encourage eligible clients to participate in colorectal cancer screening (CRCS) at primary care facilities. Additionally, it emphasizes the good outcomes of utilizing nudge in primary healthcare settings by reflecting on the novel experience of family physicians and nurses in the field of CRCS. Nudge is a cost-effective intervention that serves as a choice architect to assist people in making wise decisions for their lives. It is a subtly changed environment or combination of words that push individuals to make a decision without restricting their alternatives. This is a six-month, pragmatic trial with open-label recruitment that enrolled people with an average CRC risk from four screening healthcare zones that included 34 public primary care facilities. The study protocol is registered and can be accessed here: https://clinicaltrials.gov/ct2/show/NCT05785975. An obvious increase in the proportion of the uptake of CRCS screening is higher in the two intervention sites-Al Hait General Hospital Zone (38%) and Al-Shamli General Hospital Zone (26%), than in the two control sites, Bagaa General Hospital Zone (18%) and King Khalid Hospital Zone (18%). Using the nudge strategy to increase CRCS uptake is valuable and effective; additionally, front-line family physicians and nurses in primary care are encouraged to use a planned, positive, and highly selective set of words when offering screening. Policymakers could make use of these research outcomes when designing new guidelines for CRCS.

MTHFR Gene C677T Polymorphism (rs1801133) and Susceptibility to Colorectal Polyps in an Azerbaijani Population.

Understanding the relationships between the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, colorectal polyps, and CRC risk can aid in advancing personalized medicine approaches in CRC prevention. The aim of the current study is to identify the association of C677T polymorphism of the MTHFR gene with the risk of colorectal polyps in the Azerbaijani population. This study included 125 patients with colon polyps and 155 healthy individuals as a control group. DNA was extracted from venous blood samples obtained from patients and healthy individuals, and the results were analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis. Wild-type, heterozygote, and homozygous mutant were revealed within 69 (55.2%), 49 (39.2%), and 7 (5.6%) patients and within 100 (64.5%), 45 (29%), and 10 (6.5%) healthy controls, respectively. However, no significant statistical associations were observed between CT and TT genotypes, dominant (CC vs. CT + TT) and recessive (CC + CT vs. TT) models, and the mutant T allele and disease risk. There were also no significant differences between patients and controls regarding age, sex, smoking and alcohol use. Our research did not reveal any significant association between the MTHFR C677T polymorphism and susceptibility to colorectal polyps in the Azerbaijan population.

Serum copper status of patients with colorectal cancer: A systematic review and meta-analysis

BackgroundColorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and a public health problem. Several clinical studies have shown that copper (Cu) is involved in carcinogenesis, possibly via cuproptosis, a new form of programmed cell death, but the conclusions from published reports are inconsistent.This study aimed at evaluating the potential of Cu dysregulation as a CRC susceptibility factor. MethodsIn this systematic review and meta-analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum Cu concentrations in CRC patients and controls from articles published till June 2023. The studies included reported measurements of serum/plasma/blood Cu levels. Meta-analyses were performed as well as study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary standardized mean differences (SMDs) and the corresponding 95% confidence intervals (95% CIs) were applied to compare the levels of Cu between CRC patients and controls. Results26 studies with a pooled total of9628 participants and 2578 CRC cases were included. The pooled SMD was equal to 0.85 (95% CIs −0.44; 2.14) showing that the CRC patients had higher mean Cu levels than the control subjects, but the difference was not significant (p = 0.185) and the heterogeneity was very high, I2 = 97.9% (95% CIs: 97.5–98.3%; p < 0.001). ConclusionThe pooled results were inconclusive, likely due to discordant results and inaccuracy in reporting data of some studies; further research is needed to establish whether Cu dysregulation might contribute to the CRC risk and whether it might reflect different CRC grades.

Proteome-wide analysis reveals potential therapeutic targets for Colorectal cancer: a two-sample mendelian randomization study

BackgroundColorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting an unmet clinical need for more effective therapies. This study aims to evaluate the causal relationship between 4,489 plasma proteins and CRC to identify potential therapeutic targets for CRC.MethodsWe conducted two-sample Mendelian randomization (MR) analysis to examine the causal effects of plasma proteins on CRC. Mediation analysis was performed to assess the indirect effects of plasma proteins on CRC through associated risk factors. In addition, we conducted a phenome-wide association study using the UK Biobank dataset to examine associations between these plasma proteins and other phenotypes.ResultsOut of 4,489 plasma proteins, MR analysis revealed causal associations with CRC for 23 proteins, including VIMP, MICB, TNFRSF11B, C5orf38 and SLC5A8. Our findings also confirm the associations between reported risk factors and CRC. Mediation analysis identified mediating effects of proteins on CRC outcomes through risk factors. Furthermore, MR analysis identified 154 plasma proteins are causally linked to at least one CRC risk factor.ConclusionsOur study evaluated the causal relationships between plasma proteins and CRC, providing a more complete understanding of potential therapeutic targets for CRC.