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Oxysterols are metabolites of cholesterol that regulate the homeostasis of cholesterol, fatty acids, and glucose. These metabolites are generated throughout the body, either enzymatically or from oxidative stress, and are detectable in peripheral circulation. We previously reported that circulating 27-hydroxycholesterol (27-OHC), an endogenous selective estrogen receptor modulator, may be a risk factor for colorectal adenomas. Here, in addition to 27-OHC, we report on four other circulating oxysterols: 25-hydroxycholesterol, 24(S)-hydroxycholesterol, 7ɑ-hydroxycholesterol, and 4β-hydroxycholesterol. Oxysterol concentrations were measured using liquid chromatography/mass spectrometry from fasting plasma collected at baseline from 1,246 participants of the Vitamin D/Calcium Polyp Prevention Study, a multicenter adenoma chemoprevention trial. To evaluate multiple oxysterols simultaneously, we used both log-linear regression and Bayesian kernel machine regression models developed for analyses of complex mixtures adjusted for potential confounding factors. Higher circulating 7ɑ-hydroxycholesterol was associated with higher adenoma risk (Bayesian kernel machine regression-based multivariable-adjusted risk ratios (RR; for the 75th vs. 25th percentile, 1.22; 95% credible interval, CI, 1.04-1.42). In contrast, higher circulating 4β-hydroxycholesterol was associated with lower risk of these polyps (RR, 0.84; 95% CI, 0.71-0.99). The positive association with advanced adenoma risk that we previously reported for circulating 27-OHC persisted when controlling for other oxysterols (RR, 1.26; 95% CI, 0.98-1.62), including among those with advanced adenomas at baseline (RR, 1.75; 95% CI, 1.01-3.06). Prevention Relevance: Circulating concentrations of multiple oxysterols measured at the time of an initial colorectal adenoma diagnosis may be risk factors for subsequent incidence of these lesions. Novel colorectal cancer prevention strategies may target oxysterol formation., (©2024 American Association for Cancer Research.)

Polyphenols are plant metabolites with potential anti-inflammatory and anti-proliferative effects, which may be advantageous for disorders like colorectal cancer (CRC). Despite promising in vitro and in vivo evidence, human clinical trials have yielded mixed results. The present study aimed to evaluate the clinical evidence of polyphenols for CRC prevention or treatment. A systematic review was performed according to PRISMA. Based on a PROSPERO registered protocol (CRD42024560044), online databases (PubMed and COCHRANE) were utilized for the literature search. A total of 100 studies articles were initially identified. After reviewing, 12 studies with a low risk of bias were selected, examining the effect of a variety of compounds. Curcumin demonstrated promise in various trials, mainly decreasing inflammatory cytokines, though results varied, and it did not lower intestinal adenomas or improve outcomes after chemotherapy. Neither epigallocatechin gallate nor artepillin C reduced the incidence of adenomas. Finally, fisetin seemed to improve the inflammatory status of patients under chemotherapy (5-fluorouracil). In summary, although certain polyphenols appear to exert some effect, their role in the prevention or treatment of CRC is inconclusive, and more clinical studies under more controlled conditions are needed.

Background/aims: : The gut microbiome has emerged as a key player that mechanistically links various risk factors to colorectal cancer (CRC) etiology. However, the role of the gut microbiome in CRC pathogenesis remains unclear. This study aimed to characterize the gut microbiota in healthy controls (HCs) and patients with colorectal adenoma (AD) and CRC in subgroups based on sex and age., Methods: : Study participants who visited the hospital for surveillance of CRC or gastrointestinal symptoms were prospectively enrolled, and the gut microbiome was analyzed based on fecal samples., Results: : In terms of HC-AD-CRC sequence, commensal bacteria, including lactate-producing ( Streptococcus salivarius ) and butyrate-producing ( Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium hallii ) bacteria, were more abundant in the HC group than in the AD and CRC groups. In the sex comparison, the female HC group had more lactate-producing bacteria ( Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Lactobacillus ruminis ) than the male HC group. In age comparison, younger subjects had more butyrate-producing bacteria ( Agathobaculum butyriciproducens and Blautia faecis ) than the older subjects in the HC group. Interestingly, lactate-producing bacteria ( B. catenulatum ) were more abundant in females than males among younger HC group subjects. However, these sex- and age-dependent differences were not observed in the AD and CRC groups., Conclusions: : The gut microbiome, specifically lactate- and butyrate-producing bacteria, which were found to be abundant in the HC group, may play a role in preventing the progression of CRC. In particular, lactate-producing bacteria, which were found to be less abundant in healthy male controls may contribute to the higher incidence of CRC in males.

The incidence and mortality of colorectal cancer (CRC) have decreased through regular screening colonoscopy, surveillance, and endoscopic treatment. However, CRC can still be diagnosed after negative colonoscopy. Such CRC is called interval CRC and accounts for 1.8-9.0% of all CRC cases. Most cases of interval CRC originate from missed lesions and incompletely resected lesions. Interval CRC can be minimized by improving the quality of colonoscopy. This has led to a growing interest in and demand for high-quality colonoscopy. It is important to reduce the risk of CRC and its associated mortality by improving the quality of colonoscopy. In this review article, we provide an overview of colonoscopy quality indicators, including bowel preparation adequacy, the cecal intubation rate, the adenoma detection rate, the colonoscopy withdrawal time, appropriate polypectomy, and complication of the procedure. Because colonoscopy is a highly endoscopist-dependent procedure, colonoscopists should be well-acquainted with quality indicators and strive to apply them in daily clinical practice for the prevention of CRC.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Colorectal adenomas have the potential of malignant transformation if left untreated. Multiple randomized controlled trials have been performed to evaluate the efficacy of aspirin in preventing colorectal adenoma recurrence in a population with a history of colorectal adenoma but not colorectal cancer, however, the relationship between aspirin dose and colorectal adenoma recurrence remains unclear. We conducted pairwise meta-analysis, meta-regression, trial sequential analysis, and network meta-analysis of all eligible studies. The ROB 2.0 tool was used to assess the risk of bias in the studies. The confidence in network meta-analysis (CINeMA) approach was used to evaluate the confidence of the network meta-analysis results. The network meta-analysis included eight RCTs (nine reports), comprising four on aspirin (low or high dose) alone and four on aspirin combined with another medication, all compared with placebo. In the network meta-analysis, low-dose aspirin (LDA <300 mg per day) was more effective than high-dose aspirin (HDA ≥300 mg per day) and placebo, with risk ratios of 0.76 (95% CI: 0.58 to 0.99) and 0.7 (95% CI: 0.54 to 0.91), respectively. LDA was the optimal treatment relative to HDA and placebo (P-score = 0.99). In the trial sequential analysis, LDA was only more effective than placebo when the number of included participants exceeded the optimal information size; this was not the case for HDA. LDA has statistically significant efficacy for colorectal adenoma prevention, but compared with HDA, its efficacy remains uncertain. Further trials are therefore required., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hoang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anticancer effects of vitamin E (tocopherols) have been studied extensively. While in vitro and animal studies showed promising results regarding anticancer effects of tocopherols, human intervention studies failed to reproduce these results. In vivo , α-tocopherol (α-TOH) is metabolized to the long-chain metabolites (LCM) 13'-hydroxychromanol (α-13'-OH) and 13'-carboxychromanol (α-13'-COOH), which likely reach the large intestine. The LCM showed antiproliferative effects in different colon cancer cell lines, but the exact mechanism of action remains unclear. To further clarify the chemopreventive action of the LCM, premalignant LT97 colon adenoma cells were treated with α-TOH, α-13'-OH and α-13'-COOH to study their impact on growth, apoptosis, antigenotoxicity, and ROS-scavenging capacity as well as expression of selected genes involved in detoxification and the cell cycle. Growth inhibitory potential was observed for α-13'-OH (IC 50 : 37.4 μM) and α-13'-COOH (IC 50 : 5.8 μM) but not for α-TOH in the tested concentrations. Levels of caspase-3 activity and expression of genes regulating the cell cycle and detoxification remained unchanged. However, α-TOH, α-13'-OH and α-13'-COOH exhibited antigenotoxic and partly ROS-scavenging capacity. The results indicate that the LCM exert chemopreventive effects via ROS-scavenging capacity, the protection against DNA damage and the induction of cell death via caspase-independent mechanisms in premalignant colon cells.

Background: The onset of colorectal adenomas (CRAs) is significantly associated with colorectal cancer. The preventive effects of chemical drugs on the recurrence of CRAs have been evaluated in a large number of randomized controlled trials (RCTs). However, there are still uncertainties about the relative effectiveness of such chemical drugs., Methods: We searched relevant RCTs published in six databases up to February 2023. The quality of the included studies was assessed by using the Cochrane risk of bias assessment tool and Review Manager 5.4. Pairwise comparison and network meta-analysis (NMA) were conducted using RStudio to compare the effects of chemical drugs on the recurrence of CRAs., Results: Forty-five high-quality RCTs were included. A total of 35 590 (test group: 20 822; control group: 14 768) subjects with a history of CRAs have been enrolled and randomized to receive placebo treatment or one of 24 interventions. Based on surface under the cumulative ranking values and NMA results, difluoromethylornithine (DFMO) + Sulindac significantly reduced the recurrence of CRAs, followed by berberine and nonsteroidal antiinflammatory drugs., Conclusion: DFMO + Sulindac is more effective in reducing the recurrence of CRAs but has a high risk of adverse events. Considering drug safety, tolerance, and compliance, berberine has a brighter prospect of clinical development. However, further studies are needed to verify our findings., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78-0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66-0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55-0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women., (© 2023 UICC.)

The Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine are put forward by Nanjing University of Chinese Medicine and approved by China Association of Chinese Medicine. According to the formulation processes and methods of relevant clinical practice guidelines, the experts in clinical medicine and methodology were organized to discuss the key problems to be addressed in the clinical prevention and treatment of colorectal adenoma(CRA) and provided answers following the evidence-based medicine method, so as to provide guidance for clinical decision-making. CRA is the major precancerous disease of colorectal cancer. Although the prevention and treatment with integrated Chinese and western medicine have been applied to the clinical practice of CRA, there is still a lack of high-quality guidelines. Four basic questions, 15 clinical questions, and 10 outcome indicators were determined by literature research and Delphi questionnaire. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries, and finally several RCTs meeting the inclusion criteria were included. The data extracted from the RCT was imported into RevMan 5.3 for evidence synthesis, and the evidence was evaluated based on the Grading of Recommendations, Assessment, Development, and Evaluations(GRADE). The final recommendations were formed by the nominal group method based on the evidence summary table. The guidelines involve the diagnosis, screening, treatment with integrated Chinese and western medicine, prevention, and follow-up of colorectal adenoma, providing options for the clinical prevention and treatment of CRA.

Background: Colorectal cancer is one of the leading cancers worldwide and in Vietnam. Adenomas are important precursors of colorectal cancer. Study on the association between sleep duration and development of colorectal adenoma (CRA) is limited, particularly among Vietnamese population., Methods: We conducted an individually matched case-control study of 870 CRA cases and 870 controls in a large-scale colorectal screening program involving 103,542 individuals ages ≥40 years old in Hanoi, Vietnam. Sleep duration was categorized in three groups: short: ≤6 hours/day, normal: 7 to 8 hours/day, and long: >8 hours/day. Conditional logistic regression was used to evaluate the association between sleep duration and adenomas risk after controlling for potential confounders., Results: Overall, short-sleep duration was associated with increased risk of having CRA compared with normal duration [OR, 1.48; 95% confidence interval (CI), 1.12-1.97]. This pattern was present in both females (OR, 1.58; 95% CI, 1.14-2.18) and males (OR, 1.45; 95% CI, 1.08-1.93), with advanced adenomas (OR, 1.61; 95% CI, 1.09-2.38) and non-advanced adenomas (OR, 1.66; 95% CI, 1.19-2.32). Furthermore, the association between CRA development and short-sleep duration was more apparent among females who were nondrinker, nonobese, physically active, with proximal or both sided adenomas and with cardiometabolic disorder. Among males, the short-sleep duration was associated with CRA risk among never-smoking, cardiometabolic disorders, and obese., Conclusions: Short-sleep duration was associated with increased prevalence of both advanced and non-advanced CRAs among Vietnamese population., Impact: Findings from this study showed that maintaining an adequate sleep duration may have an important implication for colorectal adenoma prevention and control., (©2023 American Association for Cancer Research.)

Background: The possible protective effect of aspirin on risk of colorectal cancer (CRC) is still highly debated., Methods: We used data from Bowel Cancer Screening in Norway, a trial randomizing individuals from general population, aged 50-74 years, to flexible sigmoidoscopy or faecal immunochemical test (FIT), to study the association between aspirin use and detection of CRC and two CRC precursors: adenomas and advanced serrated lesions (ASL). Prescriptions of low-dose aspirin were obtained from Norwegian prescription database. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Among 64,889 screening participants (24,159 sigmoidoscopy, 40,730 FIT), 314 (0.5%) had CRC, 6,208 (9.6%) adenoma and 659 (1.0%) ASL. Overall and short-term use (<3 years) of low-dose aspirin, versus no use, were not associated with any colorectal lesion. Long-term use (≥3 years) was associated with lower detection of CRC (overall OR 0.66, 95%CI 0.46-0.93; sigmoidoscopy: 0.56, 0.33-0.97; FIT: 0.72, 0.45-1.15), adenomas in sigmoidoscopy arm (overall OR 0.95, 95%CI 0.87-1.03; sigmoidoscopy: 0.89, 0.80-0.99; FIT: 1.03, 0.89-1.18), but not ASLs. We did not observe significant differences in the effect of aspirin according to the location of colorectal lesions., Conclusion: Our results suggest that long-term use of aspirin might have a protective effect against adenomas and colorectal cancer, but not ASLs., Competing Interests: Declaration of Competing Interest The authors declare no potential conflict of interests. This study was funded by the Norwegian Research Council (project number: 301628). The funders had no role in the design of the study, the data collection, the analysis or interpretation of the data, or the writing of the article., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Lynch syndrome (LS) screening guidelines originally recommended colonoscopy every 1 to 2 years, beginning between the ages of 20 and 25 years. Recent studies have questioned the benefits of these short screening intervals in preventing colorectal cancer (CRC). Our goal is to determine how colonoscopy screening intervals impact CRC in patients with LS., Methods: We analyzed the demographics, screening practices, and outcomes of patients with LS identified through the clinic based Familial Gastrointestinal Cancer Registry at the Zane Cohen Centre, Sinai Health System, Toronto, Canada., Results: A total of 429 patients with LS were identified with median follow-up of 9.2 years; 44 developed CRC. We found a positive trend between shorter screening intervals and the number of adenomas detected during colonoscopy. Any new adenoma detected at screening decreased 10-year CRC incidence by 11.3%. For MLH1 carriers, a screening interval of 1-2 years vs 2-3 years led to a 20-year cumulative CRC risk reduction of 28% and 14% in females and males, respectively. For MSH2 carriers, this risk reduction was 29% and 17%, respectively, and for male MSH6 carriers 18%. Individuals without any adenomas detected (53.4% of LS carriers) had an increased 20-year CRC risk of 25.7% and 57.2% for women and men, respectively, compared with those diagnosed with adenomas at screening., Conclusions: The recommended colonoscopy screening interval of 1-2 years is efficient at detecting adenomas and reducing CRC risk. The observation that 53.4% of LS patients never had an adenoma warrants further investigation about a possible adenoma-free pathway., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation., Patients and Methods: Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0., Results: Fifty-three participants received the MUC1 vaccine and 50 placebo. Thirteen of 52 (25%) MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range, 2.9-17.3) at week 12 versus 0/50 placebo recipients (one-sided Fisher exact P < 0.0001). Of 13 responders at week 12, 11 (84.6%) responded to a booster injection at week 52 with a ≥2-fold increase in MUC1 IgG measured at week 55. Recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group versus 27 of 48 (56.3%) in the MUC1 group [adjusted relative risk (aRR), 0.83; 95% confidence interval (CI), 0.60-1.14; P = 0.25]. Adenoma recurrence occurred in 3/11 (27.3%) immune responders at week 12 and week 55 (aRR, 0.41; 95% CI, 0.15-1.11; P = 0.08 compared with placebo). There was no difference in serious adverse events., Conclusions: An immune response was observed only in vaccine recipients. Adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence compared with placebo was observed in participants who had an immune response at week 12 and with the booster injection., (©2023 American Association for Cancer Research.)

Colorectal cancer (CRC) is one of the deadliest forms of cancer worldwide. CRC development occurs mainly through the adenoma-carcinoma sequence, which can last decades, giving the opportunity for primary prevention and early detection. CRC prevention involves different approaches, ranging from fecal occult blood testing and colonoscopy screening to chemoprevention. In this review, we discuss the main findings gathered in the field of CRC chemoprevention, focusing on different target populations and on various precancerous lesions that can be used as efficacy evaluation endpoints for chemoprevention. The ideal chemopreventive agent should be well tolerated and easy to administer, with low side effects. Moreover, it should be readily available at a low cost. These properties are crucial because these compounds are meant to be used for a long time in populations with different CRC risk profiles. Several agents have been investigated so far, some of which are currently used in clinical practice. However, further investigation is needed to devise a comprehensive and effective chemoprevention strategy for CRC.

Background: Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents., Methods: We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study., Results: Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo., Conclusions: Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence., Registration: PROSPERO, No. CRD42022296376., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: The BeWEL randomised controlled trial (RCT) of weight loss in people with colorectal adenomas demonstrated that a significant proportion of people are interested in lifestyle interventions (49%) and clinically relevant changes in body weight were achieved at 12-month follow-up. The current work aimed to assess the feasibility of the BeWEL programme invitation and delivery in a nonresearch setting to assess whether the original results could be replicated., Methods: The original BeWel programme was modified through the provision of verbal introductions (vs. letter), requirement for people to contact BeWEL team (vs. BeWEL team contacting them), community delivery (vs. home), duration (12 weeks vs. 12 months) and two intervention visits (vs. 3) and inclusion of people with predisposition to colorectal cancer. Eligible people were informed about the BeWel programme from National Health Service (NHS) staff after colonoscopy procedures and invited to contact a dedicated Bowel Cancer UK lifestyle team., Results: Findings demonstrated that programme uptake (10.6% vs. 33%) and retention (71% vs. 93%) was significantly lower than that obtained from the BeWEL RCT. For people who participated in the 3-month programme (n = 21), self-reported weight loss (mean: -7% body weight) was successful, and the programme was well received., Conclusions: The current approach to engaging clients with the BeWEL programme is unsustainable. Reliance on busy NHS staff to deliver invitations and the need for people to contact the delivery team (due to data protection) may have impacted on uptake. Alternative approaches to supporting weight management in this population should be explored further., (© 2022 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Importance: Variants in the vitamin D-binding protein (DBP) gene (GC) encode DBP isoforms that may affect vitamin D metabolism. However, whether these isoforms modify the effects of vitamin D3 and/or calcium supplementation on colorectal adenoma recurrence is unclear. We hypothesized that supplementation effects may be stronger among those with the DBP2 isoform (encoded by the rs4588*A allele), which is associated with vitamin D deficiency and modified the associations of circulating vitamin D with risk for colorectal neoplasms in observational studies., Objective: To estimate supplemental vitamin D3 and/or calcium effects on colorectal adenoma recurrence according to 3 common DBP isoforms (DBP1s, DBP1f, DBP2) encoded by 2 missense variants: rs7041 (NG&#95;012837.3:g.57904T>G NP&#95;001191235.1:p.Asp432Glu) and rs4588 (NG&#95;012837.3:g.57915C>A NP&#95;001191235.1:p.Thr436Lys)., Design, Setting, and Participants: Secondary analysis of a randomized, double-blind, placebo-controlled clinical trial of 2259 participants with a recently diagnosed adenoma and no remaining polyps after complete colonoscopy in the US from July 1, 2004, to August 31, 2013. The current analyses were performed from August 12, 2019, to July 16, 2022., Interventions: Daily vitamin D3 (1000 IU), calcium (1200 mg), both, or placebo., Main Outcomes and Measures: One or more adenomas diagnosed during 3 to 5 years of follow-up. Treatment effects were estimated according to DBP isoform as risk ratios (RRs) and 95% CIs using Poisson regression analysis., Results: Of the 2259 participants randomized (mean [SD] age, 58 [6.8] years; 1033 [64%] men), 1604 non-Hispanic White participants (chosen to avoid population stratification bias) were included in the analysis. Among those with the DBP2 isoform (rs4588*AC or AA), the RRs (95% CI) for adenoma recurrence were 0.84 (0.72-1.00) with vitamin D3 relative to no vitamin D3, 0.83 (95% CI, 0.70-0.99) with calcium relative to no calcium, and 0.76 (95% CI, 0.59-0.98) with both agents relative to neither agent. Conversely, among those without DBP2 (rs4588*CC), the corresponding values were 1.08 (95% CI, 0.93-1.26; P = .03 for interaction) with vitamin D3 relative to no vitamin D3, 0.98 (95% CI, 0.84-1.14; P = .37 for interaction) with calcium relative to no calcium, and 1.09 (0.88-1.36; P = .03 for interaction) with both agents relative to neither agent. Among DBP2 homozygotes (rs4588*AA), the RR for adenoma recurrence was 0.57 (95% CI, 0.31-1.08) with both agents relative to neither agent., Conclusions and Relevance: The findings of this secondary analysis of a randomized clinical trial suggest that individuals with the DBP2 isoform-encoding rs4588*A allele may particularly benefit from vitamin D3 and/or calcium supplementation for colorectal adenoma prevention., Trial Registration: ClinicalTrials.gov Identifier: NCT00153816.

Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of FAT3 gene, rs61901554, showed a suggestive association ( P  = 1.10 × 10 -6 ) and was associated with advanced adenomas in CORSA ( P  = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions ( P  = 2.00 × 10 -6 ) in the Selenium Trial and were associated with advanced adenoma in CORSA ( P  = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/β-catenin pathway leading to colorectal neoplasia.Trial Registration number: NCT00078897 (ClinicalTrials.gov).

Epidemiologic studies of diabetic patients treated with metformin identified significantly lower incidences of cancer. From this, there is growing interest in the use of metformin to treat and prevent cancer. Studies have investigated chemopreventive mechanisms including alterations in calorie intake, cancer metabolism, and cell signaling. Repurposing the drug is challenging due to its metabolic effects and non-uniform effects on different types of cancer. In our previously published studies, we observed that benzo[a]pyrene treated mice receiving metformin significantly reduced lung adenomas; however, mice had reduced weight gain. In this study, we compared chemoprevention diets with and without metformin to evaluate the effects of diet vs. effects of metformin. We also performed tandem mass spectrometry on mouse serum to assess metabolomic alterations associated with metformin treatment. In metformin cohorts, the rate of weight gain was reduced, but weights did not vary between diets. There was no weight difference between diets without metformin. Interestingly, caloric intake was increased in metformin treated mice. Metabolomic analysis revealed metabolite alterations consistent with metformin treatment. Based on these results, we conclude that previous reductions in lung adenomas may have been occurred from anticancer effects of metformin rather than a potentially toxic effect such as calorie restriction.

Background: Selenium (Se) is a trace element that has been investigated as a potential chemopreventive agent for colorectal cancer. Dietary intake of other antioxidant nutrients may modify the effect of Se., Objective: We examined the association between intake and serum concentrations of retinol, β-carotene, β-cryptoxanthin, lycopene, lutein/zeaxanthin, and α- and γ-tocopherol and the development of metachronous colorectal adenoma, and if these nutrients modified the effect of Se., Methods: We conducted a prospective study of 1874 participants from the Se Trial with data for antioxidant intake, as well as a subcohort of 508 participants with serum biomarker concentrations., Results: Statistically significantly lower odds for the development of metachronous adenoma were observed for those participants in the highest tertile of intake for lutein/zeaxanthin compared to the lowest, with an OR (95% CI) of 0.72 (0.56-0.94). No effect modification for intake of any nutrient was observed. However, circulating concentrations of lycopene exhibited statistically significant effect modification of selenium supplementation ( p  < 0.06)., Conclusion: These findings show that intake and circulating concentrations of antioxidant nutrients were not consistently associated with reduced odds for the development of metachronous lesions, although blood concentrations of lycopene may modify the effect of selenium supplementation.

Purpose: The COVID-19 pandemic resulted in a partial to total shutdown of endoscopy in many healthcare centers. This study aims to quantify the impact of the reduction in colonoscopies on colorectal cancer (CRC) detection and screening., Methods: After institutional ethics board approval, the endoscopy database at an academic tertiary-care center in Montreal, Canada, was searched for all colonoscopies performed from during the first wave locally (March-June 2020), and during the ramp up period where endoscopy service resumed (July to August 2020). We compared these periods to the same periods in 2019, the pre-pandemic periods. The indications, CRC and adenoma detection rates, as well as the prioritization of urgent procedures were compared., Results: In the first wave, only 462 colonoscopies were performed, compared to 2515 in the same period in 2019, an 82% reduction. The ramp up period saw 843 colonoscopies performed compared to 1328 in 2019, a 35% reduction. Urgent and inpatient colonoscopies numbers increased (324 (24.8%) vs. 220 (5.7%)) while surveillance and high-risk screening colonoscopies fell (376 (28.8%) vs 1869 (48.6%)). Emergency access to colonoscopy was preserved with a median time to endoscopy of < 1 day (IQR 0,1) in both pandemic periods. During the pandemic periods, there was an absolute reduction in CRC diagnosis of 28, despite the CRC detection per colonoscopy rate increasing slightly in the first wave from 1.7% (44) to 3.9% (18), and in the ramp up period from 2.5% (33) to 3.6% (31). The rate of adenoma detection per colonoscopy did not increase significantly between the pre- and pandemic periods, resulting in reduction in adenoma removal in 723 patients., Discussion: The restriction of access to colonoscopy resulted in a significant reduction in screening and surveillance of high-risk patients, adenomas removed, and CRCs diagnosed. Clinicians and patients will face the oncologic ramifications this the coming years., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aspirin (acetylsalicylic acid, ASA) is inexpensive and is established in preventing cardiovascular disease (CVD) and colorectal adenomas. Omega-3 (n3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have also shown benefit in preventing CVD. The combination could be an effective preventative measure in patients with such diseases. ASA and n3 PUFA reduced the risk of CVD in ASA-resistant or diabetic patients. EPA- and DHA-deficient patients also benefited the most from n3 PUFA supplementation. Synergistic effects between ASA and EPA and DHA are 'V-shaped' such that optimal ASA efficacy is dependent on EPA and DHA concentrations in blood. In colorectal adenomas, ASA (300 mg/d) and EPA reduced adenoma burden in a location- and subtype-specific manner. Low doses of ASA (75-100 mg/d) were used in CVD prevention; however, ultra-low doses (30 mg/d) can also reduce thrombosis. EPA-to-DHA ratio is also important with regard to efficacy. DHA is more effective in reducing blood pressure and modulating systemic inflammation; however, high-dose EPA can lower CVD events in high-risk individuals. Although current literature has yet to examine ASA and DHA in preventing CVD, such combination warrants further investigation. To increase adherence to ASA and n3 PUFA supplementation, combination dosage form may be required to improve outcomes.

Aspirin has been shown to prevent the onset of colorectal adenoma and cancer. This study aimed to identify patient characteristics and blood chemistry factors related to the effect of aspirin. A total of 231 men and 59 women who participated in our previous randomized clinical study in 2007-2009 using aspirin or placebo (J-CAPP study) were analyzed. Interaction of aspirin with age at entry, body mass index (BMI), alcohol intake, blood biochemistry, and nutrients calculated from a semiquantitative food frequency questionnaire were analyzed on the basis of the presence of adenomas 2 years later. Our study showed that suppression of adenoma by aspirin was not affected by age or BMI. Among men, significant suppression of adenoma by aspirin was seen with triglyceride (TG) <167 mg/dL (P = 0.02), total cholesterol (T-cho) ≥220 mg/dL (P = 0.01), high-density lipoprotein (HDL) ≥60 mg/dL (P < 0.01), and low-density lipoprotein (LDL) ≥140 mg/dL (P = 0.01), aspartate aminotransferase (AST) <30 IU/L (P = 0.01), alanine aminotransferase <30 IU/L (P = 0.04), and gamma-glutamyl transpeptidase <60 IU/L (P = 0.04). In addition, the interaction was significant with TG ≥/<167 mg/dL (P = 0.02), T-cho ≥/<220 mg/dL (P = 0.03), HDL ≥/<60 mg/dL (P = 0.02), LDL ≥/<140 mg/dL (P = 0.03), and AST ≥/<30 IU/L (P = 0.01). Daily nutrient intake associated with aspirin was <2,000 mg sodium (P = 0.06) and ≥850 μg retinol equivalent (P = 0.05) among men, indicating a marginal effect on adenoma suppression. No significant differences were detected among women due to the small sample size. In conclusion, lipid metabolism and liver function were correlated with the suppressive effect of aspirin on the recurrence of colorectal adenoma., Prevention Relevance: Aspirin has been shown to prevent the onset of colorectal adenoma and cancer, and its effect modifications have been analyzed. Lipid metabolism and liver function were correlated with the suppressive effect of aspirin on the recurrence of colorectal adenoma., (©2022 American Association for Cancer Research.)

Although many chemopreventive studies on colorectal tumors have been reported, no effective and safe preventive agent is currently available. We searched for candidate preventive compounds against colorectal tumor comprehensively from United States Food and Drug Administration (FDA)-approved compounds by using connectivity map (CMAP) analysis coupled with in vitro screening with colorectal adenoma (CRA) patient-derived organoids (PDOs). We generated CRA-specific gene signatures based on the DNA microarray analysis of CRA and normal epithelial specimens, applied them to CMAP analysis with 1309 FDA-approved compounds, and identified 121 candidate compounds that should cancel the gene signatures. We narrowed them down to 15 compounds, and evaluated their inhibitory effects on the growth of CRA-PDOs in vitro. We finally identified resveratrol, one of the polyphenolic phytochemicals, as a compound showing the strongest inhibitory effect on the growth of CRA-PDOs compared with normal epithelial PDOs. When resveratrol was administered to Apc Min/+ mice at 15 or 30 mg/kg, the number of polyps (adenomas) was significantly reduced in both groups compared with control mice. Similarly, the number of polyps (adenomas) was significantly reduced in azoxymethane-injected rats treated with 10 or 100 mg/resveratrol compared with control rats. Microarray analysis of adenomas from resveratrol-treated rats revealed the highest change (downregulation) in expression of LEF1, a key molecule in the Wnt signaling pathway. Treatment with resveratrol significantly downregulated the Wnt-target gene (MYC) in CRA-PDOs. Our data demonstrated that resveratrol can be the most effective compound for chemoprevention of colorectal tumors, the efficacy of which is mediated through suppression of LEF1 expression in the Wnt signaling pathway., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background and Objectives: Aberrant crypt foci (ACF) are one of the earliest putative preneoplastic and, in some cases, neoplastic lesions in human colons. Many studies have confirmed the reduction of ACFs and colorectal adenomas after treatment with acetylsalicylic acid (ASA) commonly referred to as ASA; however, the minimum effective dose of ASA and the duration of use has not been fully elucidated. The objective of our study was to assess the significance of low dose ASA (75-mg internally once daily) to study the chemopreventive effect of ASA in ACF and adenomas development in patients taking this drug for a minimum period of 10 years. Materials and Methods: Colonoscopy, combined with rectal mucosa staining with 0.25% methylene blue, was performed on 131 patients. The number of rectal ACF in the colon was divided into three groups: ACF < 5; ACF 5−10; and ACF > 10. Patients were divided into two groups: the “With ASA” group (the study group subjects taking ASA 75-mg daily for 10 years); and “Without ASA” group (control group subjects not taking ASA chronically). The incidence of different types of rectal ACF and colorectal polyps in both groups of subjects was analysed and ascertained. Results: Normal ACF was found in 12.3% in the study group vs. 87.7% control group, hyperplastic 22.4% vs. 77.6%, dysplastic 25% vs. 75%, mixed 0% vs. 100%. Treatment with ASA affects the occurrence of colorectal adenomas. The amount of dysplastic ACFs was lower in the study group than in the control group. The increase in dysplastic ACFs decreases with age in both groups, with the increase greater in those not taking ASA. Conclusions: Patients who take persistent, chronic (>10 years) low doses of ASA have a lower total number of all types of rectal ACFs and adenomas compared to the control group.

Objective: To observe the inhibitory effect of Shenbai Jiedu Fang (SBJDF, a compound recipe of traditional Chinese herbal drugs) on chemically induced carcinogenesis of colorectal adenoma in mice and explore the role of PTEN/PI3K/AKT signaling pathway in mediating this effect., Methods: Four-week-old male C57BL/6 mice were randomly divided into control group ( n =10), AOM/DSS model group ( n =20), low-dose (14 g/kg) SBJDF group ( n =10) and high-dose (42 g/kg) SBJDF group ( n = 10). In the latter 3 groups, the mice were treated with azoxymethane (AOM) and dextran sodium sulphate (DSS) to induce carcinogenesis of colorectal adenoma. In the two SBJDF treatment groups, SBJDF was administered daily by gavage during the modeling. The survival rate, body weight, general condition of the mice, and intestinal adenoma formation and carcinogenesis were observed. The expressions of proteins associated with the PTEN/PI3K/AKT signaling pathway in the intestinal tissue were detected using immunohistochemistry., Results: Compared with those in the model group, the mice treated with SBJDF, especially at the high dose, showed a significantly lower incidence of intestinal carcinogenesis and had fewer intestinal tumors with smaller tumor volume. Pathological examination showed the occurrence of adenocarcinoma in the model group, while only low-grade and high-grade neoplasia were found in low-dose SBJDF group; the mice treated with high-dose SBJDF showed mainly normal mucosal tissues in the intestines with only a few lesions of low-grade neoplasia of adenoma. Compared with those in the control group, the mice in the model group had significantly elevated plasma miRNA-222 level ( P < 0.05), which was obviously lowered in the two SBJDF groups ( P < 0.01). The results of immunohistochemistry revealed that compared with the model group, the two SBJDF groups, especially the high-dose group, had significantly up-regulated expressions of PTEN, P-PTEN and GSK-3β and down-regulated expressions of p-GSK-3 β, PI3K, AKT, P-AKT, β-catenin, c-myc, cyclinD1 and survivin in the intestinal tissues., Conclusion: SBJDF can significantly inhibit colorectal adenoma formation and carcino-genesis in mice possibly through regulating miRNA-222 and affecting PTEN/PI3K/AKT signaling pathway.

Background: The study sought to conduct a systematic review and meta-analysis of the risk of colorectal adenoma or cancer in patients with microscopic colitis (MC)., Methods: A comprehensive literature search of PubMed and EMBASE databases was performed. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to examine the effect of MC on the risk of colorectal adenoma or cancer., Results: Twelve studies reporting the outcomes of 50 795 patients with MC were eligible for this meta-analysis. MC was negatively associated with the risk of colorectal adenoma compared with participants without MC (RR, 0.44; 95% CI, 0.33-0.58; P < .001; I2 = 87.3%). Also, the rate of colorectal cancer was lower in the patients with MC compared with the general population (RR, 0.62; 95% CI, 0.43-0.89; P = .01; I2 = 91.6%). In addition, sensitivity and subgroup analyses indicated that the results were robust., Conclusions: The present systematic review indicated that patients with MC may be associated with a lower risk of colorectal adenoma or cancer. The clinical data support the current professional society guideline. A surveillance colonoscopy program is not recommended as standard for patients with MC., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Chemoprevention for colorectal neoplasia has attracted growing interest, with multiple medications investigated. Metformin may decrease the overall incidence of cancer in patients with diabetes and may decrease the incidence of colorectal cancer., Aims: We aimed to determine the impact of metformin use on the behavior of colorectal adenomas in a US veteran population., Methods: All patients with at least two high-quality colonoscopies between January 1997 and December 2013 at Veterans Affairs New York Harbor Healthcare System were identified. Outpatient prescription records were used to determine metformin exposure, and colonoscopy findings were recorded. Multivariable logistic regression was used to determine factors associated with adenoma detection on baseline and interval colonoscopy., Results: In total, 1869 patients with two successive colonoscopies (median 4.5 years) were included. Four hundred and sixty patients had metformin exposure prior to baseline and/or interval colonoscopy. Overall adenoma detection rate was 59.7% at baseline and 45.9% at interval colonoscopy. On multivariable analysis, metformin use was associated with decreased adenoma prevalence at baseline (OR 0.68; 95% CI 0.51-0.92; p = 0.015). Metformin did not impact adenoma incidence at interval colonoscopy whether prescribed before baseline (OR 1.26; 95% CI 0.60-2.67), after baseline (OR 1.25; 95% CI 0.91-1.72), or before and after baseline (OR 1.14; 95% CI 0.82-1.58)., Conclusions: In this retrospective analysis of an average-risk cohort, metformin use was associated with a decreased prevalence of colorectal adenomas at baseline colonoscopy. This inverse association did not persist on interval colonoscopy. Prospective studies are needed to evaluate potential chemoprotective effects of metformin over time., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Introduction: Diet may affect bile acid (BA) metabolism and signaling. In turn, BA concentrations may be associated with cancer risk. We investigated (i) associations of BA concentrations with adenoma recurrence and (ii) the effect of a high-fiber, high-fruit and vegetable, and low-fat dietary intervention on serum BA concentrations., Methods: The Polyp Prevention Trial is a 4-year randomized, controlled trial that investigated the effect of a high-fiber, high-fruit and vegetable, and low-fat diet on colorectal adenoma recurrence. Among 170 participants who reported adhering to the intervention and 198 comparable control arm participants, we measured 15 BAs in baseline, year 2, and year 3 serum using targeted, quantitative liquid chromatography-tandem mass spectrometry. We estimated associations of BAs with adenoma recurrence using multivariable logistic regression and the effect of the dietary intervention on BA concentrations using repeated-measures linear mixed-effects models. In a subset (N = 65), we investigated associations of BAs with 16S rRNA gene sequenced rectal tissue microbiome characteristics., Results: Baseline total BA concentrations were positively associated with adenoma recurrence (odds ratio Q3 vs Q1 = 2.17; 95% confidence interval = 1.19-4.04; Ptrend = 0.03). Although we found no effect of the dietary intervention on BA concentrations, pretrial dietary fiber intake was inversely associated with total baseline BAs (Spearman = -0.15; PFDR = 0.02). BA concentrations were associated with potential colorectal neoplasm-related microbiome features (lower alpha diversity and higher Bacteroides abundance)., Discussion: Baseline circulating BAs were positively associated with adenoma recurrence. Although the dietary intervention did not modify BA concentrations, long-term fiber intake may be associated with lower concentrations of BAs that are associated with higher risk of adenoma recurrence., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Colorectal cancer (CRC) is the fourth most common cancer and third leading cause of cancer-related death worldwide. Use of chemopreventive agents (CPAs) to reduce the incidence of precursor colorectal adenomas could lower the future burden of CRC. Many classes of potential CPAs have been investigated. To identify the most effective CPAs, we conducted a systematic review and a network meta-analysis (NMA). An electronic search was performed through August 2020 to identify all randomized controlled trials (RCTs) assessing the efficacy of CPAs in reducing the incidence of colorectal adenomas at the time of surveillance colonoscopy among patients who had previously undergone polypectomy during an index colonoscopy. In total, 33 RCTs were included in the NMA, which was conducted under a Bayesian inference framework. Random effects models were used with adjustment for follow-up length and control group event rates to yield relative risks (RRs) and 95% credible intervals (CrIs). Our full network consisted of 13 interventions in addition to a placebo arm. Of 20,925 included patients, 7766 had an adenoma. Compared to placebo, the combination of difluoromethylornithine (DFMO) + Sulindac (RR 0.24, CrI 0.10-0.55) demonstrated a protective effect, while aspirin had a RR of 0.77 (CrI 0.60-1.00), celecoxib 800 mg had a RR of 0.56 (CrI 0.31-1.01) and metformin had a RR of 0.56 (CrI 0.22-1.39). Our results suggest that select CPAs may be efficacious in preventing the development of adenomas. Further studies are needed to identify those patients most likely to benefit and the minimum effective dosages of CPAs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) is the third most common cancer in both sexes and the second in terms of mortality. Apart from genetic predisposition, dietary and lifestyle factors have been implicated in the development of CRC. Several studies suggested that vitamin D (VitD) might be a promising strategy in CRC prevention, while other studies did not confirm this finding. The aim of our study was to examine the role of Vit-D supplementation in the prevention of colorectal neoplasms (CRC and polyps). We conducted a systematic search in Pubmed, Embase and Web of Science databases for Randomized Controlled Trials (RCTs) examining the incidence of colorectal neoplasms in patients taking Vit-D supplementation compared to placebo. We synthetized results using Risk Ratio along with 95% Confidence Intervals (CIs). Nine RCTs (N = 71,386) were included. Non-significant correlations were observed between Vit-D supplementation and CRC incidence (RR:1.06, p = 0.52). Similarly, non-significant associations were observed between the use of Vit-D supplements and colorectal adenoma incidence (RR:1.00, p = 0.91). Advanced adenomas (OR:1.05, p = 0.63) and serrated polyps (RR:1.03, p = 0.63) were also not significantly inversely associated with Vit-D supplementation. Our study shows that Vit-D does not seem to have a role in the chemoprevention of colorectal neoplasms. However, additional well-designed studies are needed in order to draw safe conclusions. A potentially beneficial role of Vit-D supplementation in CRC primary prevention in individuals with severe vitamin D deficiency as well in the primary prevention of early-onset CRC, requires further investigation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: AGA guidelines emphasize split-dose bowel preparation (BP) to ensure high-quality colonoscopy for the prevention of colorectal cancer (CRC). Split dose results in higher-quality preparation, but understanding instructions might be more difficult. Lower education levels may negatively influence BP quality. The confounding role of education level on BP quality was investigated., Methods: This was a cross-sectional study of 60 patients given split-dose BP. Patients consented and were asked three Likert scale questions based on BP instructions before the procedure. Compliance was self-reported. BP adequacy and the number of adenomas were recorded. BP was characterized as adequate (excellent, good) or inadequate (fair, poor). Data was analyzed with chi-square, odds ratio, Mann-Whitney, and regression analysis., Results: Thirty-one (52%) patients were high school graduates, 21 (38%) completed some college, and 6 (10%) were college graduates. College-educated patients had adequate BP (72%) more often than high school graduates (51%) (p = 0.02). Adenoma findings were not significantly different. The Likert scale mean ranks for patient understanding and reviewing of instructions were comparable between the two groups. Patient rating of scheduler explanations of the importance of following instructions was significantly better in the college group (mean ranks 2.59 and 1.83, respectively; p = 0.018)., Discussion: Patient education level significantly affected the success of BP. Split BP can be more complex to comprehend, and instructions should consider patient education level. Specific intervention programs should be implemented to advise patients with less education that poor preparation may result in missed advanced neoplasias and subsequent procedures., (© 2021. American Association for Cancer Education.)

Background and Aim: Surveillance colonoscopies may be delayed because of pressure on resources, such as the COVID-19 pandemic. This study aimed to determine whether delayed surveillance colonoscopy increases the risk for advanced neoplasia and whether interval screening with faecal immunochemical tests (FITs) and other known risk factors can mitigate this risk., Methods: A retrospective cohort study of individuals undergoing surveillance colonoscopy for personal or family history of colorectal neoplasia was being provided with FIT between colonoscopies. Colonoscopy ≥ 6 months after the guideline-recommended interval was considered "delayed." Individuals were stratified based on prime colonoscopy findings to nonneoplastic findings, non-advanced adenoma, and advanced adenoma. The relative risk (RR) for developing advanced neoplasia was determined using a robust multivariable modified Poisson regression., Results: Of 2548 surveillance colonoscopies, 1457 (57.18%) were delayed. Prior advanced adenoma, older age (> 60 years) and nonparticipation in interval FIT were associated with increased risk for advanced neoplasia (P < 0.05). There was a trend to increased risk in those with prior advanced adenoma with an increasing colonoscopy delay (P trend = 0.01). In participants who did not complete interval FIT and having advanced adenoma in the prime colonoscopy, risk of advanced neoplasia was 2.48 times higher (RR = 2.48, 95% confidence interval: 1.20-5.13) in participants who had beyond 2 years of delayed colonoscopy compared with those with on-time colonoscopy. Colonoscopy delay did not increase the risk of advanced neoplasia in participants with negative interval FIT results., Conclusion: Surveillance colonoscopy can be safely extended beyond 6 months in elevated colorectal cancer risk patients who do not have prior advanced adenoma diagnosis, particularly if interval FIT is negative., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Preclinical, epidemiological, and small clinical studies suggest that green tea extract (GTE) and its major active component epigallocatechingallate (EGCG) exhibit antineoplastic effects in the colorectum., Methods: A randomized, double-blind trial of GTE standardized to 150 mg of EGCG b.i.d. vs placebo over 3 years was conducted to prevent colorectal adenomas (n = 1,001 with colon adenomas enrolled, 40 German centers). Randomization (1:1, n = 879) was performed after a 4-week run-in with GTE for safety assessment. The primary end point was the presence of adenoma/colorectal cancer at the follow-up colonoscopy 3 years after randomization., Results: The safety profile of GTE was favorable with no major differences in adverse events between the 2 well-balanced groups. Adenoma rate in the modified intention-to-treat set (all randomized participants [intention-to-treat population] and a follow-up colonoscopy 26-44 months after randomization; n = 632) was 55.7% in the placebo and 51.1% in the GTE groups. This 4.6% difference was not statistically significant (adjusted relative risk 0.905; P = 0.1613). The respective figures for the per-protocol population were 54.3% (151/278) in the placebo group and 48.3% (129/267) in the GTE group, indicating a slightly lower adenoma rate in the GTE group, which was not significant (adjusted relative risk 0.883; P = 0.1169)., Discussion: GTE was well tolerated, but there was no statistically significant difference in the adenoma rate between the GTE and the placebo groups in the whole study population., (Copyright © 2022 by The American College of Gastroenterology.)

Background/aims: The worldwide coronavirus disease 2019 pandemic has led endoscopists to use personal protective equipment (PPE) for infection prevention. This study aimed to investigate whether wearing a face shield as PPE affects the quality of colonoscopy., Methods: We reviewed the medical records and colonoscopy findings of patients who underwent colonoscopies at Asan Medical Center, Korea from March 10 to May 31, 2020. The colonoscopies in this study were performed by five gastroenterology fellows and four expert endoscopists. We compared colonoscopy quality indicators, such as withdrawal time, adenoma detection rate (ADR), mean number of adenomas per colonoscopy (APC), polypectomy time, and polypectomy adverse events, both before and after face shields were added as PPE on April 13, 2020., Results: Of the 1,344 colonoscopies analyzed, 715 and 629 were performed before and after the introduction of face shields, respectively. The median withdrawal time was similar between the face shield and no-face shield groups (8.72 minutes vs 8.68 minutes, p=0.816), as was the ADR (41.5% vs 39.8%, p=0.605) and APC (0.72 vs 0.77, p=0.510). Polypectomy-associated quality indicators, such as polypectomy time and polypectomy adverse events were also not different between the groups. Quality indicators were not different between the face shield and no-face shield groups of gastroenterology fellows, or of expert endoscopists., Conclusions: Colonoscopy performance was not unfavorably affected by the use of a face shield. PPE, including face shields, can be recommended without a concern about colonoscopy quality deterioration.

Despite mounting evidence that dietary factors might have a protective role against risk of cancer, few studies have assessed the relationship between diet diversity with colorectal cancer (CRC) and colorectal adenoma (CRA). Thus, we examined the relationship between dietary diversity score (DDS) and the odds of CRC and CRA. Overall, 129 CRC diagnosed patients, 130 CRA diagnosed cases and 240 healthy hospitalised controls were studied. DDS was calculated based on information on the usual diet that was assessed by a valid and reliable food frequency questionnaire (FFQ). Multivariate logistic regression was used to estimate the relationship between DDS and odds of colorectal cancer and adenoma. After adjusting for potential confounders, the diversity of grains is associated with the increased odds of CRC (OR grains : 2·96 (1·05-8·32); P = 0·032), while the diversity of vegetables and fruits are associated with decreased odds of CRC (OR vegetables : 0·31 (0·16-0·62); P = 0·001, OR fruits : 0·37 (0·23-0·61); P < 0·001). The diversity of vegetables, fruits and dairy are inversely associated with odds of CRA (OR vegetables : 0·41 (0·21-0·78); P = 0·007, OR fruits : 0·58 (0·36-0·93); P = 0·021, OR dairies : 0·56 (0·37-0·83); P = 0·004). Also, higher DDS was related to decreased odds of both CRC (OR: 0·41 (0·23-0·72); P for trend = 0·002) and CRA (OR: 0·36 (0·21-0·65); P for trend = 0·001). Our results indicated that higher dietary diversity and particularly a diet varied in fruits and vegetables may reduce the odds of CRC and CRA. Also, the consumption of dairy products may decrease the odds of CRC, whereas the consumption of grains may increase the odds of CRC., (© The Author(s) 2022.)

Background: Colonoscopy surveillance is recommended for some patients post polypectomy. The 2002 UK surveillance guidelines classify post-polypectomy patients into low, intermediate and high risk, and recommend different strategies for each classification. Limited evidence supports these guidelines., Objectives: To examine, for each risk group, long-term colorectal cancer incidence by baseline characteristics and the number of surveillance visits; the effects of interval length on detection rates of advanced adenomas and colorectal cancer at first surveillance; and the cost-effectiveness of surveillance compared with no surveillance., Design: A retrospective cohort study and economic evaluation., Setting: Seventeen NHS hospitals., Participants: Patients with a colonoscopy and at least one adenoma at baseline., Main Outcome Measures: Long-term colorectal cancer incidence after baseline and detection rates of advanced adenomas and colorectal cancer at first surveillance., Data Sources: Hospital databases, NHS Digital, the Office for National Statistics, National Services Scotland and Public Health England., Methods: Cox regression was used to compare colorectal cancer incidence in the presence and absence of surveillance and to identify colorectal cancer risk factors. Risk factors were used to stratify risk groups into higher- and lower-risk subgroups. We examined detection rates of advanced adenomas and colorectal cancer at first surveillance by interval length. Cost-effectiveness of surveillance compared with no surveillance was evaluated in terms of incremental costs per colorectal cancer prevented and per quality-adjusted life-year gained., Results: Our study included 28,972 patients, of whom 14,401 (50%), 11,852 (41%) and 2719 (9%) were classed as low, intermediate and high risk, respectively. The median follow-up time was 9.3 years. Colorectal cancer incidence was 140, 221 and 366 per 100,000 person-years among low-, intermediate- and high-risk patients, respectively. Attendance at one surveillance visit was associated with reduced colorectal cancer incidence among low-, intermediate- and high-risk patients [hazard ratios were 0.56 (95% confidence interval 0.39 to 0.80), 0.59 (95% confidence interval 0.43 to 0.81) and 0.49 (95% confidence interval 0.29 to 0.82), respectively]. Compared with the general population, colorectal cancer incidence without surveillance was similar among low-risk patients and higher among high-risk patients [standardised incidence ratios were 0.86 (95% confidence interval 0.73 to 1.02) and 1.91 (95% confidence interval 1.39 to 2.56), respectively]. For intermediate-risk patients, standardised incidence ratios differed for the lower- (0.70, 95% confidence interval 0.48 to 0.99) and higher-risk (1.46, 95% confidence interval 1.19 to 1.78) subgroups. In each risk group, incremental costs per colorectal cancer prevented and per quality-adjusted life-year gained with surveillance were lower for the higher-risk subgroup than for the lower-risk subgroup. Incremental costs per quality-adjusted life-year gained were lowest for the higher-risk subgroup of high-risk patients at £7821., Limitations: The observational design means that we cannot assume that surveillance caused the reductions in cancer incidence. The fact that some cancer staging data were missing places uncertainty on our cost-effectiveness estimates., Conclusions: Surveillance was associated with reduced colorectal cancer incidence in all risk groups. However, in low-risk patients and the lower-risk subgroup of intermediate-risk patients, colorectal cancer incidence was no higher than in the general population without surveillance, indicating that surveillance might not be necessary. Surveillance was most cost-effective for the higher-risk subgroup of high-risk patients., Future Work: Studies should examine the clinical effectiveness and cost-effectiveness of post-polypectomy surveillance without prior classification of patients into risk groups., Trial Registration: This trial is registered as ISRCTN15213649., Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 26. See the NIHR Journals Library website for further project information.

Aspirin intake has been shown to lead to significant protection against colorectal cancer, for example with an up to twofold reduction in colorectal adenoma incidence rates at higher doses. The mechanisms contributing to protection are not yet fully understood. While aspirin is an anti-inflammatory drug and can thus influence the tumor microenvironment, in vitro and in vivo experiments have recently shown that aspirin can also have a direct effect on cellular kinetics and fitness. It reduces the rate of tumor cell division and increases the rate of cell death. The question arises whether such changes in cellular fitness are sufficient to significantly contribute to the epidemiologically observed protection. To investigate this, we constructed a class of mathematical models of in vivo evolution of advanced adenomas, parameterized it with available estimates, and calculated population level incidence. Fitting the predictions to age incidence data revealed that only a model that included colonic crypt competition can account for the observed age-incidence curve. This model was then used to predict modified incidence patterns if cellular kinetics were altered as a result of aspirin treatment. We found that changes in cellular fitness that were within the experimentally observed ranges could reduce advanced adenoma incidence by a sufficient amount to account for age incidence data in aspirin-treated patient cohorts. While the mechanisms that contribute to the protective effect of aspirin are likely complex and multi-factorial, our study demonstrates that direct aspirin-induced changes of tumor cell fitness can significantly contribute to epidemiologically observed reduced incidence patterns., Competing Interests: YW, CB, AG, DW, NK No competing interests declared, (© 2022, Wang et al.)

Background: The influence of anthropometric characteristics on colorectal neoplasia biology is unclear. We conducted a systematic review and meta-analysis to determine if adult-attained height is independently associated with the risk of colorectal cancer or adenoma., Methods: We searched MEDLINE, EMBASE, the Cochrane Library, and Web of Science from inception to August 2020 for studies on the association between adult-attained height and colorectal cancer or adenoma. The original data from the Johns Hopkins (Baltimore, MD) Colon Biofilm study was also included. The overall HR/OR of colorectal cancer/adenoma with increased height was estimated using random-effects meta-analysis., Results: We included 47 observational studies involving 280,644 colorectal cancer and 14,139 colorectal adenoma cases. Thirty-three studies reported data for colorectal cancer incidence per 10-cm increase in height; 19 yielded an HR of 1.14 [95% confidence interval (CI), 1.11-1.17; P < 0.001), and 14 engendered an OR of 1.09 (95% CI, 1.05-1.13; P < 0.001). Twenty-six studies compared colorectal cancer incidence between individuals within the highest versus the lowest height percentile; 19 indicated an HR of 1.24 (95% CI, 1.19-1.30; P < 0.001), and seven resulting in an OR of 1.07 (95% CI, 0.92-1.25; P = 0.39). Four studies reported data for assessing colorectal adenoma incidence per 10-cm increase in height, showing an overall OR of 1.06 (95% CI, 1.00-1.12; P = 0.03)., Conclusions: Greater adult attained height is associated with an increased risk of colorectal cancer and adenoma., Impact: Height should be considered as a risk factor for colorectal cancer screening., (©2022 American Association for Cancer Research.)

Ethnopharmacological Relevance: Berberine(BBR) is a kind of isoquinoline alkaloids extracted from the rhizomes of Coptis chinensis Franch., which was the main active ingredient. Accumulating evidence has shown that it has potential pharmacological effects in preventing the recurrence of colorectal adenomas., Aim of the Study: The roles of BBR in the overall recurrence of colorectal adenoma have still not been assessed because of the limitations of the available data and the restriction of a single study. Therefore, we evaluated the effectiveness and safety of BBR in preventing the recurrence of colorectal adenomas through a systematic review and meta-analysis of available data., Materials and Methods: We searched four English databases (PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials (CENTRAL), Embase and Web of Science) and four Chinese language databases (Chinese Biomedicine (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP) and the WanFang Database) from their inception through October 2020. Meta-analysis was performed with RevMan5.3 software after data extraction and the quality of studies assessment., Results: Three randomized controlled clinical trials were included with 1076 patients. Our results illustrated that 1-year and 2-year supplementation with BBR was associated with lower recurrence rate of colorectal adenoma (RR 0.69, 95% CI 0.57 to 0.84, p=0.0001; RR 0.75, 95% CI 0.64 to 0.88, p=0.0004). The relative risk of oral BBR for 1 year and 2 years is not comparable, for 2-year efficacy outcomes were assessed in all participants who had at least one colonoscopy with pathological evaluation after baseline (lots of participants completed the first colonoscopy but discontinued during the second follow-up interval.). Moreover, the results also suggest that BBR had more adverse events than placebo (RR 2.91, 95% CI 1.24 to 6.85, p=0.01). Through the full-text reading, no serious adverse events were observed, and constipation was the most common event which disappears once the drug is discontinued., Conclusion: Generally, the present study indicated that BBR has a comparable therapeutic effect on the prevention of colorectal adenomas recurrence. Adverse reactions are worthy of attention which requires additional studies to obtain a precise conclusion., Prospero Registration No: CRD42020209135., (Copyright © 2021. Published by Elsevier B.V.)

The risk of transition to colorectal cancer (CRC) in advanced colorectal adenomas (ACAs) is about 2.5 times higher than the non-advanced ones. This systematic review and meta-analysis was performed to determine the effect of calcium and dairy products on the incidence of CAs and ACAs. Six databases were systematically searched and 37 relevant clinical trials and observational studies involving over 10,964 cases were selected for inclusion. The results showed that calcium consumption reduced the risk of CAs incidence by 8% (RR: 0.92; 95% CI: 0.89-0.96), and calcium intake as a food and dairy product reduced it about 21% (RR: 0.79; 95% CI: 0.72-0.86), and 12% (RR: 0.88; 95% CI: 0.78-0.98), respectively. However, calcium supplementation did not show a significant effect on CAs incidence (RR: 0.97; 95% CI: 0.89-1.05). Results also revealed that total calcium intake markedly reduced the risk of ACAs (RR: 0.79; 95% CI: 0.73-0.85) and the risk of recurrence of adenomas about 12% (RR: 0.88; 95% CI: 0.84-0.93). Our results suggest that natural sources of calcium such as dairy products and foods may have more effective role than supplementary calcium in terms of reducing the risk of incidence and recurrence of colorectal adenomas and advanced adenomas.

Dietary fiber intake has been suggested to decrease the risks of colorectal cancer (CRC) and adenoma. This cross-sectional study aimed to evaluate the association between total dietary fiber intake and colorectal adenoma among asymptomatic Korean adults. Individuals who received a screening colonoscopy between May and December of 2011 were recruited. Multivariable-adjusted logistic regression was used to assess the odds ratios (ORs) and 95% confidence intervals (CIs) of colorectal adenoma. 558 of the 1,716 study participants were diagnosed with colorectal adenoma. No significant association between total dietary fiber intake and colorectal adenoma was found; ORs (95% CIs) for subsequent quintiles compared to the bottom quintile were 1.00 (0.69-1.46), 1.11 (0.73-1.71), 0.97 (0.57-1.65), and 0.88 (0.46-1.71; P for trend = 0.65). Dietary fiber intakes from cereal, fruit, vegetable, or legume weren't associated with colorectal adenoma. When we compared >30 g/d to ≤10 g/d of total dietary fiber intake, OR (95% CI) was 0.32 (0.10-1.02; P for trend = 0.23). In the analyses of advanced or high-risk state and location of adenoma, we didn't observe significant associations. In conclusion, dietary fiber intake was not associated with colorectal adenoma in Korean adults. However, the association for low intake of dietary fiber warrants further investigation.

Metformin is an old, inexpensive, and relatively safe anti-diabetic medication that can decrease the risk of several types of cancer in patients with diabetes. Recent meta-analyses have revealed that metformin markedly decreased the incidence of colorectal adenoma, advanced adenoma, and colorectal cancer (CRC) among patients with diabetes. Potential mechanisms by which metformin may decrease colorectal cancer risk include its effects on ameliorating intestinal inflammation and dysbiosis, suppressing major proliferative pathways, preventing DNA replication, accelerating tumor cells apoptosis, inhibiting intra-tumor angiogenesis and epithelial-mesenchymal transition (EMT), increasing tumor-infiltrating lymphocytes and CD68+ tumor-associated macrophages, and enhancing T cells cytotoxic activity. It is well-known that metformin can improve overall survival and CRC-specific survival among patients with diabetes and CRC. Interestingly, metformin decreases the incidence of colonic adenoma in patients with acromegaly and reduces the incidence of inflammatory bowel disease (IBD) among patients with diabetes, which can indirectly lower the risk of CRC. Results of phase II clinical trials have revealed that metformin can enhance the anti-cancer effects of chemotherapeutic agents, such as 5-Fluorouracil (5-FU) and irinotecan on refractory CRC. Furthermore, metformin decreases the risk of new polyps and adenomas in patients without diabetes. Regarding the results of previous preclinical and clinical studies, it is rational to assess the effect of metformin in normoglycemic patients with CRC and expand its clinical application for treating CRC or preventing it in a high-risk population., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This paper introduces a recent paper on colorectal cancer prevention studies using aspirin. Aspirin was shown to reduce the colorectal cancer under the age of 50, and on a large scale of cohort study with long-term tracking reported that aspirin was shown to reduce colorectal cancer, gastric cancer, and esophageal cancer as well. Also, in a randomized clinical trial in Lynch syndrome reported that aspirin was shown to reduce the colorectal cancer with long-term tracking; and in a randomized trial in familial adenomatous polyposis, reported that aspirin was shown to reduce the increase of colorectal polyp. In addition, we introduced a hypothesis on the mechanism of colorectal cancer prevention by aspirin. Based on these latest findings, we proposed an aspirin administration method to prevent colorectal cancer.

Colorectal cancer causes over 53,000 deaths annually in the United States. Its rising incidences worldwide and particularly in young adults is a major concern. Here, we evaluated the efficacy of omeprazole that is clinically approved for treating acid reflux, to enable its repurposing for colorectal cancer prevention. In the azoxymethane-induced rat colorectal cancer model, dietary omeprazole (250 and 500 ppm) was administered at early adenoma stage (8 weeks after azoxymethane) to assess the progression of early lesions to adenocarcinoma. Administration of omeprazole at 250 or 500 ppm doses led to suppression of total colon adenocarcinoma incidence by 15.7% and 32% ( P < 0.01), respectively. Importantly, invasive carcinoma incidence was reduced by 59% ( P < 0.0005) and 90% ( P < 0.0001) in omeprazole-administered rats in a dose-dependent manner. There was also a strong and dose-dependent inhibition in the adenocarcinoma multiplicity in rats exposed to omeprazole. Administration of 250 and 500 ppm omeprazole inhibited total colon adenocarcinoma multiplicity by approximately 49% and approximately 65% ( P < 0.0001), respectively. While noninvasive adenocarcinomas multiplicity was suppressed by approximately 34% to approximately 48% ( P < 0.02), the invasive carcinomas multiplicity was reduced by approximately 74% to approximately 94% ( P < 0.0001) in omeprazole-exposed rats in comparison with the untreated rats. Biomarker analysis results showed a decrease in cell proliferation and anti-apoptotic/pro-survival proteins with an increase in apoptosis. Transcriptome analysis of treated tumors revealed a significant increase in adenocarcinoma inhibitory genes (Olmf4; Spink4) expression and downregulation of progression promoting genes (SerpinA1, MMP21, IL6). In summary, omeprazole showed significant protection against the progression of adenoma to adenocarcinoma. PREVENTION RELEVANCE: Preventing colon cancer is urgently needed because of its high incidence and mortality rates worldwide. Toward this end, preventive efficacy of omeprazole, a common medication, was evaluated in animal model of colorectal cancer and was found to suppress colonic adenoma progression to carcinoma. These findings warrant its further evaluation in humans., (©2021 American Association for Cancer Research.)

In recent decades, significant progress has been made in the diagnosis and treatment of colorectal carcinomas. Prevention and early detection with endoscopic therapy are of central importance. With the introduction of national screening programs, the early detection of adenomas and small tumors during colonoscopy has been significantly improved, thus reducing the incidence of colorectal carcinoma. In Germany, for example, this has been reduced by 17-26 % since its introduction in 2002. Thus, primary and secondary prevention are of considerable importance, although the annual uptake in Germany for screening Kolonoscopy is still only between 1.9 and 4.4 % and for stool test use between 8.6 and 27.1 %. We present here the importance of primary and secondary prevention based on pathogenesis, risk factors and diagnostic and therapeutic endoscopic options., Competing Interests: Arthur Schmidt erhielt Vortragshonorare und Forschungs-Unterstützung von Ovesco Endoscopy., (Thieme. All rights reserved.)