Risk Of Colorectal Cancer Research Articles

Incidence of late recurrence and second primary cancers 5-10 years after non-metastatic colorectal cancer.

The fraction of patients who are cancer-free survivors 5 years after curative-intended surgery for colorectal cancer (CRC) is increasing, suggesting that extending surveillance beyond 5 years may be indicated. Here we estimate the incidence of late recurrence, metachronous CRC, and second primary cancers 5-10 years postoperative. All patients resected for UICC stage I-III CRC in Denmark through 2004-2013 were identified. Through individual-level linkage of nationwide health registry data, recurrence status was determined using a validated algorithm. Cancer-free survivors 5 years after surgery, were included. Cumulative incidence functions (CIF) of late recurrence, metachronous CRC, and second primary cancer 5-10 years postoperative were constructed. Subdistribution hazards ratios (sHR) were computed using Fine-Gray regression. Among 8883 patients, 370 developed late recurrence (5-10-year CIF = 4.1%, 95%CI: 3.7%-4.6%), 270 metachronous CRC (5-10-year CIF = 3.0%, 95%CI: 2.7%-3.4%), and 635 a second primary cancer (5-10-year CIF = 7.2%, 95%CI: 6.7%-7.7%). The risk of late recurrence was reduced for patients operated in 2009-2013 compared to 2004-2008 (2.9% vs. 5.6%, sHR = 0.52, 95% CI: 0.42-0.65). The risk of metachronous CRC was likewise reduced from 4.1% to 2.1% (sHR = 0.50, 95%CI: 0.39-0.65). While the risk of second primary cancer did not change between 2009-2013 and 2004-2008 (7.1% vs. 7.1%, sHR = 0.98, 95% CI: 0.84-1.15). Using nation-wide 10-year follow-up data, we document that the incidences of late recurrence and metachronous CRC are low and decreasing from 2004 to 2013. Thus, despite increasing numbers of long-term cancer survivors, the data do not advocate for extending CRC-specific surveillance beyond 5 years.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer.

Colorectal cancer (CRC) is a serious threat worldwide. Although early screening is suggested to be the most effective method to prevent and control CRC, the current situation of early screening for CRC is still not optimistic. In China, the incidence of CRC in the Yangtze River Delta region is increasing dramatically, but few studies have been conducted. Therefore, it is necessary to develop a simple and efficient early screening model for CRC. To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC. Data of 64448 participants obtained from Ningbo Hospital, China between 2014 and 2017 were retrospectively analyzed. The cohort comprised 64448 individuals, of which, 530 were excluded due to missing or incorrect data. Of 63918, 7607 (11.9%) individuals were considered to be high risk for CRC, and 56311 (88.1%) were not. The participants were randomly allocated to a training set (44743) or validation set (19175). The discriminatory ability, predictive accuracy, and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic (ROC) curves and calibration curves and by decision curve analysis. Finally, the model was validated internally using a bootstrap resampling technique. Seven variables, including demographic, lifestyle, and family history information, were examined. Multifactorial logistic regression analysis revealed that age [odds ratio (OR): 1.03, 95% confidence interval (CI): 1.02-1.03, P < 0.001], body mass index (BMI) (OR: 1.07, 95%CI: 1.06-1.08, P < 0.001), waist circumference (WC) (OR: 1.03, 95%CI: 1.02-1.03 P < 0.001), lifestyle (OR: 0.45, 95%CI: 0.42-0.48, P < 0.001), and family history (OR: 4.28, 95%CI: 4.04-4.54, P < 0.001) were the most significant predictors of high-risk CRC. Healthy lifestyle was a protective factor, whereas family history was the most significant risk factor. The area under the curve was 0.734 (95%CI: 0.723-0.745) for the final validation set ROC curve and 0.735 (95%CI: 0.728-0.742) for the training set ROC curve. The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population. The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age, BMI, WC, lifestyle, and family history exhibited high accuracy.

Analysis of 1999–2017 NHANES Data: Minimal Increase and Racial Disparities in U.S. Fiber Consumption Over 18 Years

Low dietary fiber consumption is associated with an increased risk of colorectal cancer, a leading cause of cancer-related mortality in the United States. The average daily fiber intake has declined over recent decades. Notably, Black Americans exhibit lower fiber consumption than other racial/ethnic groups, possibly influencing their elevated colorectal cancer rates. We hypothesize that there has been a significant increase in dietary fiber consumption in the United States from 1999 to 2017. The study encompassed 59,204 adult NHANES participants and observed variations in caloric intake over survey years. Although there was a slight overall increase in dietary fiber intake compared to 1999, the most substantial increment occurred among individuals classified as Hispanic (AD: +2.86 g, P < 0.001), followed by non-Hispanic Black (AD: +1.64 g, P < 0.001), and finally non-Hispanic White showed a decrease in fiber intake (AD: −0.86 g, P < 0.001). The findings suggest a modest rise in fiber consumption from 1999 to 2017, but disparities persist, particularly with non-Hispanic Black individuals consuming the least fiber. This emphasizes the need for interventions to promote fiber intake and address racial/ethnic inequalities in dietary habits.

Managing Colorectal Cancer from Ethology to Interdisciplinary Treatment: The Gains and Challenges of Modern Medicine.

Colorectal cancer (CRC) is a common malignant tumor of the gastrointestinal tract, which has become a serious threat to human health worldwide. This article exhaustively reviews colorectal cancer's incidence and relevance, carcinogenesis molecular pathways, up-to-date treatment opportunities, prophylaxis, and screening program achievements, with attention paid to its regional variations and changes over time. This paper provides a concise overview of known CRC risk factors, including familial, hereditary, and environmental lifestyle-related risk factors. The authors take a closer look into CRC's molecular genetic pathways and the role of specific enzymes involved in carcinogenesis. Moreover, the role of the general practitioner and multidisciplinary approach in CRC treatment is summarized and highlighted based on recent recommendations and experience. This article gives a clear understanding and review of the gains and challenges of modern medicine towards CRC. The authors believe that understanding the current patterns of CRC and its revolution is imperative to the prospects of reducing its burden through cancer prevention and cancer-adjusted treatment.

Screening and surveillance for hereditary colorectal cancer.

Hereditary colorectal cancer is a type of cancer that is caused by a genetic mutation. Individuals with a family history of colorectal cancer, or who have a known hereditary syndrome, are at an increased risk of developing the disease. Screening and surveillance are important tools for managing the risk of hereditary colorectal cancer. Screening involves a combination of tests that can detect precancerous or cancerous changes in the colon and rectum. Surveillance involves regular follow-up examinations to monitor disease progression and to identify new developments. The frequency and type of screening and surveillance tests may vary depending on an individual's risk factors, genetic profile, and medical history. However, early detection and treatment of hereditary colorectal cancer can significantly improve patient outcomes and reduce mortality rates. By implementing comprehensive screening and surveillance strategies, healthcare providers can help individuals at risk of hereditary colorectal cancer to receive timely interventions and make informed decisions about their health. Specific examples of screening and surveillance tests for hereditary colorectal cancer include colonoscopy, genetic testing, and imaging tests. In this review article, we will discuss detailed screening and surveillance of hereditary colorectal cancer.

Genome-Wide Interaction Study of Dietary Intake and Colorectal Cancer Risk in the UK Biobank

Candidate gene analysis approaches have shown that colorectal cancer (CRC) risk attributable to diet may differ according to genotype. A genome-wide approach further allows for the exploration of underlying pathways for associations between diet and CRC risk across the genome. To identify genetic variants that modify diet-CRC associations and to further explore the underlying pathways in the cause of CRC. This nested case-control study used data on White British participants from the prospective cohort UK Biobank. Participants were recruited between March 13, 2006, and October 1, 2010, and data were censored June 25, 2021. The average frequency intake of 11 dietary factors in the year preceding baseline was obtained via a touchscreen questionnaire. After quality control for more than 93 million variants of imputed genetic data, 4 122 345 variants remained. Colorectal cancer cases were identified according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Genome-wide interaction analysis was performed to test interactions between dietary factors and variants using a conditional logistic regression model. Summary statistics of interactions at the variant level were used to calculate empirical P values for interactions at gene and gene-set levels in gene-based and gene-set enrichment analyses. A total of 4686 participants with CRC (mean [SD] age, 60.7 [6.6] years; 2707 men [57.8%]) received a new diagnosis during a median of 12.4 years (IQR, 11.6-13.1 years) of follow-up. Once a case was detected, 3 matched controls were identified, for a total of 14 058 controls (mean [SD] age, 60.4 [6.6] years; 8121 men [57.8%]). A total of 324 variants were identified that interacted with diet consumption at the suggestive threshold (P < 1 × 10-5). In gene-based analysis, aggregation of multiple EPDR1 gene variants was found to interact with fish intake regarding CRC risk. Furthermore, gene-set enrichment analysis found that several sets of protein-coding genes, which were overrepresented with particular functions and pathways, interacted with the consumption of milk (ART), cheese (OR), tea (KRT), and alcohol (PRM and TNP). In this nested case-control study, the risk of CRC associated with fish intake was modified by multiple single-nucleotide polymorphisms of the EPDR1 gene. The findings further suggested possible functions and pathways that might link the consumption of milk, cheese, tea, and alcohol with CRC development.

Adult Height and Risk of Colorectal Cancer: A Pooled Analysis of 10 Population-based Cohort Studies in Japan.

While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07-1.40), 1.22 (95% CI, 1.09-1.36), and 1.27 (95% CI, 1.08-1.49), respectively, in men and 1.21 (95% CI, 1.09-1.35), 1.23 (95% CI, 1.08-1.40), and 1.35 (95% CI, 1.003-1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Low Colorectal Cancer Risk After Resection of High-Risk Pedunculated Polyps

IntroductionPost-Faecal Immunochemical Test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas. Due to an expected higher risk of Colorectal Cancer (CRC), post-polypectomy surveillance is recommended, generating a substantially increased load on endoscopy services. The aim of our study was to investigate post-polypectomy CRC risk in a screening population of FIT+ subjects after resection of low- (LRA) or high-risk adenomas (HRA). MethodsWe retrieved data from a cohort of patients undergoing post-polypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 and followed-up to December 2021. Main outcomes were post-polypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia and location of the index lesion. We adopted as comparators FIT+/colonoscopy negative and FIT negative patients. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables. ResultsOverall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had a LRA and 22,709 (26.0%) a HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (Hazard Ratio [HR] 1.18, 95% Confidence Interval [CI] 0.92-1.53) was not increased compared to the FIT+/colonoscopy negative group, while for HRAs a significant increase in CRC incidence (HR 1.53, 95% CI 1.14-2.04) was found. The presence of one or more risk factors among proximal location, non-pedunculated morphology and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR 1.85, 95% CI 1.36-2.52). Patients with only distal pedunculated polyps without HGD, representing 39.2% of HRA, did not have increased risk compared to the FIT-negative group (HR 0.87, 95% CI 0.59 - 1.28). ConclusionsCRC incidence is significantly higher in patients with high-risk adenomas diagnosed at colonoscopy. However, such excess risk does not appear to apply to patients with only distal pedunculated polyps without HGD, an observation that could potentially reducethe burden of surveillance in FIT programs.

Loss of symbiotic and increase of virulent bacteria through microbial networks in Lynch syndrome colon carcinogenesis.

Through a pilot study, we performed whole gut metagenomic analysis in 17 Lynch syndrome (LS) families, including colorectal cancer (CRC) patients and their healthy first-degree relatives. In a second asymptomatic LS cohort (n=150) undergoing colonoscopy-screening program, individuals with early precancerous lesions were compared to those with a normal colonoscopy. Since bacteria are organized into different networks within the microbiota, we compared related network structures in patients and controls. Fecal prokaryote DNA was extracted prior to colonoscopy for whole metagenome (n=34, pilot study) or 16s rRNA sequencing (validation study). We characterized bacteria taxonomy using Diamond/MEGAN6 and DADA2 pipelines and performed differential abundances using Shaman website. We constructed networks using SparCC inference tools and validated the construction's accuracy by performing qPCR on selected bacteria. Significant differences in bacterial communities in LS-CRC patients were identified, with an enrichment of virulent bacteria and a depletion of symbionts compared to their first-degree relatives. Bacteria taxa in LS asymptomatic individuals with colonic precancerous lesions (n=79) were significantly different compared to healthy individuals (n=71). The main bacterial network structures, constructed based on bacteria-bacteria correlations in CRC (pilot study) and in asymptomatic precancerous patients (validation-study), showed a different pattern than in controls. It was characterized by virulent/symbiotic co-exclusion in both studies and illustrated (validation study) by a higher Escherichia/Bifidobacterium ratio, as assessed by qPCR. Enhanced fecal virulent/symbiotic bacteria ratios influence bacterial network structures. As an early event in colon carcinogenesis, these ratios can be used to identify asymptomatic LS individual with a higher risk of CRC.

Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer trial study protocol: a randomised clinical trial of fibre-rich legumes targeting the gut microbiome, metabolome and gut transit time of overweight and obese patients with a history of noncancerous adenomatous polyps

IntroductionRecently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a...

Maximizing scarce colonoscopy resources: the crucial role of stool-based tests.

During the COVID-19 pandemic, health systems, including federally qualified health centers, experienced disruptions in colorectal cancer (CRC) screening. National organizations called for greater use of at-home stool-based testing followed by colonoscopy for those with abnormal test results to limit (in-person) colonoscopy exams to people with acute symptoms or who were high risk. This stool-test-first strategy may also be useful for adults with low-risk adenomas who are due for surveillance colonoscopy. We argue that colonoscopy is overused as a first-line screening method in low- and average-risk adults and as a surveillance tool among adults with small adenomas. Yet, simultaneously, many people do not receive much-needed colonoscopies. Delivering the right screening tests at intervals that reduce the risk of CRC, while minimizing patient inconvenience and procedural risks, can strengthen health-care systems. Risk stratification could improve efficiency of CRC screening, but because models that adequately predict risk are years away from clinical use, we need to optimize use of currently available technology-that is, low-cost fecal testing followed by colonoscopy for those with abnormal test results. The COVID-19 pandemic highlighted the urgent need to adapt to resource constraints around colonoscopies and showed that increased use of stool-based testing was possible. Learning how to adapt to such constraints without sacrificing patients' health, particularly for patients who receive care at federally qualified health centers, should be a priority for CRC prevention research.

The protective effect of teprenone in TNBS-induced ulcerative colitis rats by modulating the gut microbiota and reducing inflammatory response

Objective Ulcerative colitis (UC), a chronic and refractory nonspecific inflammatory bowel disease, affects millions of patients worldwide and increases the risk of colorectal cancer. Teprenone is an acylic polyisoprenoid that exerts anti-inflammatory properties in rat models of peptic ulcer disease. This in vitro and in vivo study was designed to investigate the effects of teprenone on UC and to explore the underlying mechanisms. Methods Human intestinal epithelial cells (Caco-2 cells) serve as the in vitro experimental model. Lipopolysaccharide (LPS, 1 μg/mL) was employed to stimulate the production of pro-inflammatory cytokines (interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]-α), Toll-like receptor-4 (TLR4), MyD88 expression, and NF-κB activation. A trinitrobenzene sulfonic acid (TNBS)-induced chronic UC rat model was employed for the in vivo assay. Results Pro-inflammatory cytokine stimulation by LPS in Caco-2 cells was inhibited by teprenone at 40 μg/mL through the TLR4/NF-κB signaling pathway. Teprenone attenuated TNBS-induced UC, decreased myeloperoxidase and malondialdehyde, induced TLR4 expression and NF-κB activation, and increased glutathione and zonula occludens-1 level in the rat colonic tissue. Moreover, Fusobacterium, Escherichia coli, Porphyromonas gingivalis elevation, and Mogibacterium timidum decline in UC rats were inhibited by teprenone. Conclusion Based on our results, the protective effects of teprenone for UC may be related to its ability to modulate the gut microbiota and reduce the inflammatory response.

Traditional Mexican dietary pattern and cancer risk among women of Mexican descent

PurposeTo examine the association of a traditional Mexican diet score with risk of total, breast, and colorectal cancer among women of Mexican ethnic descent in the Women’s Health Initiative (WHI).MethodsParticipants were WHI enrollees who self-identified as being of Mexican descent. Data from food frequency questionnaires self-administered at study baseline were used to calculate the MexD score, with higher scores indicating greater adherence to an a priori-defined traditional Mexican diet (high in dietary fiber, vegetables, and legumes). Incident cancers were self-reported by participants from 1993 to 2020 and adjudicated by trained physicians. We used multivariable-adjusted Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsAmong 2,343 Mexican descent women (median baseline age: 59 years), a total of 270 cancers (88 breast, 37 colorectal) occurred during a mean follow-up of 14.4 years. The highest tertile of MexD score was associated with a lower risk of all-cancer incidence (HR: 0.67; 95% CI 0.49–0.91; p-trend: 0.01) and colorectal cancer (HR: 0.38; 95% CI 0.14–0.998; p-trend < 0.05), with each unit increase in the MexD score associated with a 6% lower risk of all-cancer incidence (HR: 0.94; 95% CI 0.88–0.99). There was no statistically significant association with risk of breast cancer.ConclusionConsumption of a traditional Mexican diet was associated with a significantly lower risk of all-cancer incidence and colorectal cancer. Confirmation of these findings in future studies is important, given the prevalence of colorectal cancer and a growing U.S. population of women of Mexican descent.

Dietary Patterns and Lifestyle Factors Associated with the Risk of Colorectal Cancer: A Hospital-Based Case-Control Study among Malaysians.

This study aimed to examine the association between dietary patterns, lifestyle factors, and colorectal cancer (CRC) risk among the Malaysian population. We recruited 100 patients and 100 controls from two selected government hospitals. Principal component analysis was used to identify dietary patterns using a 123-item semiquantitative food frequency questionnaire. Tobacco smoking and alcohol consumption questionnaires were modified from the WHO STEPS Survey questionnaire. Physical activity levels were assessed using the revised Global Physical Activity questionnaire. Associations between dietary patterns, lifestyle factors and CRC risk were assessed using logistic regression with SPSS version 24.0. Three dietary patterns were derived from factor analysis: i) vegetables; ii) meat, seafood and processed food; and iii) grains and legumes. High vegetable diet intake was independently and significantly associated with an 81% decreased risk of CRC (odds ratio [OR]: 0.19; 95% confidence interval [CI]: 0.08, 0.46). Both recreational-related physical activity (OR: 2.04; 95% CI: 1.14, 3.64) and vigorous physical activity (OR: 2.06; 95% CI: 1.13, 3.74) are significantly associated with decreased risk of CRC. Increasing the number of cigarettes smoked (≥ 16 cigarettes) per day significantly increased the odds of developing CRC (OR: 2.58; 95% CI: 1.95, 6.75). The duration of alcohol consumption cessation was inversely associated with CRC risk (OR: 2.52; 95% CI: 2.30, 10.57). The protective effects of a fruit and vegetable diet, and a healthy lifestyle can be used to develop interventions that help reduce the risk of CRC in the Malaysian population.

Modifiable Risk Factors and Risk of Colorectal and Endometrial Cancers in Lynch Syndrome: A Systematic Review and Meta-Analysis.

Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancers. Modifiable risk factors, including obesity, physical activity, alcohol intake, and smoking, are well-established in sporadic cancers but are less studied in Lynch syndrome. Searches were conducted on MEDLINE, Embase, and Web of Science for cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Adjusted hazard ratios (HRs) and 95% CIs for colorectal and endometrial cancers were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462), and the meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology reporting guidelines. A total of 770 citations were reviewed. Eighteen studies were identified for qualitative synthesis, with seven colorectal cancer (CRC) studies eligible for meta-analysis. Obesity (HR, 2.38 [95% CI, 1.52 to 3.73]) was associated with increased CRC risk. There was no increased CRC risk associated with smoking (HR, 1.04 [95% CI, 0.82 to 1.32]) or alcohol intake (HR, 1.32 [95% CI, 0.97 to 1.81]). Type 2 diabetes mellitus (T2DM) and some dietary factors might increase risk of CRC although more studies are needed. In a qualitative synthesis of three endometrial cancer cohort studies, female hormonal risk factors and T2DM may affect the risk of endometrial cancer, but obesity was not associated with an increased risk. Lifestyle recommendations related to weight and physical activity may also be relevant to cancer prevention for individuals with Lynch syndrome. Further high-quality prospective cohort studies, in particular, including endometrial cancer as an end point, are needed to inform evidence-based cancer prevention strategies in this high-risk population.

Molecular Mechanisms Associated with the Inhibitory Role of Long Chain n-3 PUFA in Colorectal Cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related death in the world. Multiple evidence suggests that there is an association between excess fat consumption and the risk of CRC. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential for human health, and both in vitro and in vivo studies have shown that these fatty acids can prevent CRC development through various molecular mechanisms. These include the modulation of arachidonic acid (AA) derived prostaglandin synthesis, alteration of growth signaling pathways, arrest of the cell cycle, induction of cell apoptosis, suppression of angiogenesis and modulation of inflammatory response. Human clinical studies found that LC n-3 PUFA combined with chemotherapeutic agents can improve the efficacy of treatment and reduce the dosage of chemotherapy and associated side effects. In this review, we discuss comprehensively the anti-cancer effects of LC n-3 PUFA on CRC, with a main focus on the underlying molecular mechanisms.

Abstract B008: The polyclonal path towards malignant transformation in familial adenomatous polyposis

Abstract The widely accepted paradigm that cancer initiation is a monoclonal event has not been definitively resolved. This is largely due to the limitations of experimental systems to study cancer initiation, a definitively transient step in tumorigenesis. Individuals with familial adenomatous polyposis (FAP) possess a germline APC mutation, leading to hundreds of colonic polyps in adolescence and an eventual 100% lifetime risk of colorectal cancer. As such, total colectomies are performed once polyp burden becomes unmanageable and provide the resected colons from FAP donors provide a source of histologically normal mucosa, benign and dysplastic polyps, and, on rare occasions, adenocarcinomas, and serve as an exemplary model disease to understand human tumorigenesis. Through whole genome sequencing of 123 independent samples from six patients, we reveal the polyclonal origins of tumorigenesis in FAP. We characterize and contrast the genomic landscape and relative timing of driver mutation acquisition across normal to dysplastic and invasive colon tissue and compare this with multi-region sequencing data from sporadic colorectal cancers (CRC). We find that only early sporadic CRC drivers are common across the more heterogeneous premalignant stages. Selection, as assessed based on the ratio of nonsynonymous to synonymous mutations (dN/dS), is higher in benign than dysplastic FAP lesions and in sporadic adenomas relative to carcinomas. Phylogenetic reconstruction and pairwise sample comparisons reveal extensive heterogeneity and subclonal sharing within a patient’s benign and dysplastic lesions. Using a mechanistic mathematical model, we infer polyclonality for 90-100% of benign and 53-83% of dysplastic samples. Based on these findings, we propose a conceptual framework for the polyclonal origin of intestinal malignancies where inconsequential mutations, arising during colon formation in utero, are present across the colon and are valuable markers to uncover polyclonal ancestry. Citation Format: Ryan O. Schenck, Aziz Khan, Aaron M. Horning, Edward D. Esplin, HTAN Consortia, William J. Greenleaf, James M. Ford, Michael P. Snyder, Christina Curtis. The polyclonal path towards malignant transformation in familial adenomatous polyposis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B008.

Dynamic Prediction of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease

Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. We pooled data from six existing cohort studies from Canada, the Netherlands, the UK, and the USA. Patients with IBD and an indication for CRC surveillance were included if they underwent at least one follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modelling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. The surveillance cohorts comprised 3,731 patients, enrolled and followed-up in the time period 1973-2021, with a median follow-up of 5.7 years (26,336 patient-years of follow-up); 146 individuals were diagnosed with aCRN. The model contained eight predictors, with a cross-validation median c-statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals prior to clinical application.

Screening Perspectives: The Role of Colorectal Cancer Awareness in Shaping Attitudes Toward Colonoscopy in Palestine.

To assess colorectal cancer (CRC) awareness and its influence on attitudes toward colonoscopy in Palestine. Convenience sampling was used to recruit Palestinian adults from hospitals, primary health care centers, and public spaces across 11 governorates. To evaluate the awareness of CRC signs/symptoms, risk factors, and mythical causes, the Bowel Cancer Awareness Measure and Cancer Awareness Measure-Mythical Causes Scale were used after translation into Arabic. For each correctly recognized item, one point was given. The total awareness score of each domain was calculated and categorized into tertiles; the top tertile was considered high awareness, and the other two tertiles were considered low awareness. A total of 4,623 questionnaires were included. Only 1,849 participants (40.0%) exhibited high awareness of CRC signs/symptoms. High awareness of CRC symptoms was associated with higher likelihood of showing positive attitudes toward colonoscopy (odds ratio [OR], 1.21 [95% CI, 1.07 to 1.37]). A total of 1,840 participants (38.9%) demonstrated high awareness of CRC risk factors. Participants with high awareness of CRC risk factors were more likely to display positive attitudes toward colonoscopy (OR, 1.20 [95% CI, 1.07 to 1.37]). Only 219 participants (4.7%) demonstrated high awareness of CRC causation myths. There was no association between awareness of CRC causation myths and positive attitudes toward colonoscopy. Awareness of CRC was poor with less than half of the study participants demonstrating high awareness of CRC signs/symptoms and risk factors, and a minority (<5%) displaying high awareness of CRC causation myths. High awareness of CRC signs/symptoms and risk factors was associated with greater likelihood of demonstrating positive attitudes toward colonoscopy. Educational initiatives are needed to address knowledge gaps and dispel misconceptions surrounding CRC.

Management of colorectal cancer screening backlog due to the COVID-19 pandemic: A retrospective analysis of the use of a colorectal cancer screening clinical-decision support tool in Argentina

BackgroundThe COVID-19 pandemic created a backlog in colorectal cancer (CRC) screening and surveillance colonoscopies. The real impact in Argentina is not fully known. GoalTo estimate the impact of the COVID-19 pandemic on CRC prevention by comparing the number of CRC screening and surveillance consults in a clinical decision support-tool used in Argentina before, during and after pandemic lockdown. MethodsWe analyzed data from May 2019 to December 2021 from CaPtyVa, a clinical decision support tool for CRC screening and surveillance. Queries were divided in pre-pandemic (May 2019 to March 2020), lockdown (April 2020 to December 2020), and post-lockdown (January 2021 to December 2021). The number of CRC monthly screening and surveillance visits were compared among the three periods and stratified according to CRC risk. ResultsOverall, 27,563 consults were analyzed of which 9035 were screening and 18,528 were surveillance. Pre-pandemic, the median number of screening consults was 346 per month (IQR25–75 280–410). There was a decrease to 156 (80–210)/month (p<0.005) during lockdown that partially recovered during post-lockdown to 230 (170–290)/month (p=0.05). Pre-pandemic, the median number of surveillance consults was 716 (560–880)/month. They decreased to 354 (190–470)/month during lockdown (p<.05) and unlike screening, completely recovered during post-lockdown to 581 (450–790)/month. ConclusionsThere was a >50% decrease in the number of CRC screening and surveillance consults registered in CaPtyVa during lockdown in Argentina. Post-lockdown, surveillance consults recovered to pre-pandemic levels, but screening consults remained at 66% of pre-pandemic levels. This has implications for delays in CRC diagnoses and patient outcomes.