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Background: Adenomatous polyps are associated with an increased risk of developing colorectal cancer. Physical activity (PA) and spending less time sedentary may reduce risk of polyp recurrence and cancer incidence. This study examined associations between PA, sedentary time, and stool metabolites in adults at high risk for developing colorectal cancer. Methods: Participants were ≥18 years old with ≥1 adenomatous polyps removed in the previous 3 years. PA and sedentary time were assessed using an activPAL™ accelerometer. Stool samples were analyzed for short-chain fatty acids, and primary/secondary bile acid metabolites by mass spectrometry. Linear regression models examined associations between PA, sedentary time, and stool parameters, with dietary fiber as a covariate. Results: Participants (N = 21) were 59 (9) years old and had a body mass index of 28.1 (3.35 kg/m2). Light-intensity PA was associated with butyrate (β = 1.88; 95% confidence interval [CI], 0.477 to 3.291) and propionate (β = 1.79; 95% CI, 0.862 to 2.724). Moderate to vigorous PA was associated with deoxycholic acid (β = −6.13; 95% CI, −12.14 to −0.11) and ursodeoxycholic acid (β = −0.45; 95% CI, −0.80 to −0.12) abundance. Conclusions: Both light and moderate to vigorous PA were associated with gut microbial metabolite production. These findings suggest the importance of examining PA intensity alongside stool metabolites for colorectal cancer prevention. [ABSTRACT FROM AUTHOR]

The understanding and explanation of inflammation-dysplasia-cancer sequence is challenging. The gut microbiota is an important factor for the intestine wall. The changes in bacteria quality and/or quantity (dysbiosis) may begin the colon inflammation. This paper reviewed the gut microbiome risk factors which may lead to colon cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC), mainly because of chronic intestinal inflammation. Some unique molecular differences occur in colitis-associated CRC, resulting in a different sequence of events, primarily of inflammation–dysplasia–carcinoma, compared to sporadic cases. In this context, the recent and continuous evolution in our understanding of the genetic and molecular mechanisms underlying IBD-associated CRC and the development of new OMIC techniques has opened up new possibilities for personalised and organ-sparing therapies. This review provides an overview of the IBD-related carcinogenesis pathway with a focus on the interaction between microbiota and the gut barrier and the role of currently available therapies for IBD in the inflammation–dysplasia–cancer sequence. Patients affected by inflammatory bowel disease (IBD) have a two-fold higher risk of developing colorectal cancer (CRC) than the general population. IBD-related CRC follows a different genetic and molecular pathogenic pathway than sporadic CRC and can be considered a complication of chronic intestinal inflammation. Since inflammation is recognised as an independent risk factor for neoplastic progression, clinicians strive to modulate and control disease, often using potent therapy agents to achieve mucosal healing and decrease the risk of colorectal cancer in IBD patients. Improved therapeutic control of inflammation, combined with endoscopic advances and early detection of pre-cancerous lesions through surveillance programs, explains the lower incidence rate of IBD-related CRC. In addition, current research is increasingly focused on translating emerging and advanced knowledge in microbiome and metagenomics into personalised, early, and non-invasive CRC screening tools that guide organ-sparing therapy in IBD patients. This review aims to summarise the existing literature on IBD-associated CRC, focusing on new insights into the alteration of the intestinal barrier and the interactions with the gut microbiome as the initial promoter. In addition, the role of OMIC techniques for precision medicine and the impact of the available IBD therapeutic armamentarium on the evolution to CRC will be discussed. [ABSTRACT FROM AUTHOR]

Patients with ulcerative colitis (UC) are at a two- to three-fold increased risk of developing colorectal cancer (CRC) than the general population based on population-based data. UC-CRC has generated a series of clinical problems, which are reflected in its worse prognosis and higher mortality than sporadic CRC. Chronic inflammation is a significant contributor to the development of UC-CRC, so comprehending the relationship between the proinflammatory factors and epithelial cells together with downstream signaling pathways is the core to elucidate the mechanisms involved in developing of CRC. Clinical studies have shown the importance of early prevention, detection and management of CRC in patients with UC, and colonoscopic surveillance at regular intervals with multiple biopsies is considered the most effective way. The use of endoscopy with targeted biopsies of visible lesions has been supported in most populations. In contrast, random biopsies in patients with high-risk characteristics have been suggested during surveillance. Some of the agents used to treat UC are chemopreventive, the effects of which will be examined in cancers in UC in a population-based setting. In this review, we outline the current state of potential risk factors and chemopreventive recommendations in UC-CRC, with a specific focus on the proinflammatory mechanisms in promoting CRC and evidence for personalized surveillance. [ABSTRACT FROM AUTHOR]

More than 10 studies have confirmed the association of antibiotic overuse with colorectal cancer. The exact cause is unknown, but most authors hypothesize that disturbance of colon microbiota is the main culprit. In this commentary, an evolutionary explanation is proposed. It is well known that antibiotics can induce antibiotic resistance in bacteria through selection of mutators—DNA mismatch repair deficient (dMMR) strains. Mutators have an increased survival potential due to their high mutagenesis rate. Antibiotics can also cause stress in human cells. Selection of dMMR colon cells may be advantageous under this stress, mimicking selection of bacterial mutators. Concomitantly, mismatch repair deficiency is a common cause of cancer, this may explain the increased cancer risk after multiple cycles of oral antibiotics. This proposed rationale is described in detail, along with supporting evidence from the peer-reviewed literature and suggestions for testing hypothesis validity. Treatment schemes could be re-evaluated, considering toxicity and somatic selection mechanisms. Lay Summary The association of antibiotics with colon cancer is well established but of unknown cause. Under an evolutionary framework, antibiotics may select for stress-resistant cancerous cells that lack mechanisms for DNA mismatch repair (MMR). This mimics the selection of antibiotic resistant 'mutators'—MMR-deficient micro-organisms—highly adaptive due to their increased mutagenesis rate. [ABSTRACT FROM AUTHOR]

Although colorectal cancer (CRC) incidence in the USA is declining overall, its incidence is increasing among those younger than 50 years of age. The reasons underlying the increasing trend are largely unknown, although behavioral changes, such as unhealthy diet and lifestyle factors, may be partially responsible. A prospective cohort study included 94 217 women aged 26-45 years at baseline. Validated anthropometric measures and lifestyle information were self-reported biennially. Exposures were four recommendation-based dietary indices—the prime diet quality score and three plant-based dietary indices; and two mechanism-based indices—the empirical dietary and lifestyle index for hyperinsulinemia (EDIH and ELIH). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and for early-onset (before age 50) and after age 50 CRC separately. We documented 332 cases of CRC during 24 years of follow-up (2 113 655 person-years), with an average age of 52 ± 7 years at diagnosis. Hyperinsulinemic dietary and lifestyle patterns were associated with a higher risk of CRC. Multivariable-adjusted HRs (95% CIs) comparing participants in the highest versus lowest quartile were: 1.67 for EDIH (95% CI: 1.15-2.44, P -trend = 0.01) and 1.51 for ELIH (95% CI: 1.10-2.08, P -trend = 0.01). Moreover, per 75% increment in rank, ELIH appeared to be a stronger risk factor for early-onset CRC (HR = 1.86, 95% CI: 1.12-3.07) than after age 50 CRC (HR = 1.20, 95% CI: 0.83-1.73, P -heterogeneity = 0.16). The four recommendation-based indices were not significantly associated with overall, early-onset, or after age 50 CRC risk (per 75% increment in rank, HRs ranged from 0.75 to 1.28). Dietary and lifestyle patterns contributing to hyperinsulinemia were associated with greater CRC risk in younger women. Moreover, the hyperinsulinemic lifestyle showed a suggestively stronger positive association with early-onset CRC risk, compared with after age 50 CRC. Our findings suggest that dietary and lifestyle interventions to reduce insulinemic potential may be effective for CRC prevention among younger women. • Dietary and lifestyle patterns contributing to hyperinsulinemia were associated with higher colorectal cancer (CRC) risk in the young population. • The hyperinsulinemic lifestyle showed an even stronger positive association with early-onset CRC (age <50 at diagnosis) risk. • We elucidated the potential of modifiable factors for preventing early-onset CRC. [ABSTRACT FROM AUTHOR]

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated. [ABSTRACT FROM AUTHOR]

Alcohol is a consistently identified risk factor for colon cancer. However, the molecular mechanism underlying its effect on normal colon crypt cells remains poorly understood. We employed RNA-sequencing to asses transcriptomic response to ethanol exposure (0.2% vol:vol) in 3D organoid lines derived from healthy colon (n = 34). Paired regression analysis identified 2,162 differentially expressed genes in response to ethanol. When stratified by colon location, a far greater number of differentially expressed genes were identified in organoids derived from the left versus right colon, many of which corresponded to cell-type specific markers. To test the hypothesis that the effects of ethanol treatment on colon organoid populations were in part due to differential cell composition, we incorporated external single cell RNA-sequencing data from normal colon biopsies to estimate cellular proportions following single cell deconvolution. We inferred cell-type-specific changes, and observed an increase in transit amplifying cells following ethanol exposure that was greater in organoids from the left than right colon, with a concomitant decrease in more differentiated cells. If this occurs in the colon following alcohol consumption, this would lead to an increased zone of cells in the lower crypt where conditions are optimal for cell division and the potential to develop mutations. [ABSTRACT FROM AUTHOR]

Oxaliplatin-based adjuvant chemotherapy is the standard treatment of high-risk colon cancer (CC). A shorter duration (3 months) can achieve a similar outcome [in terms of relapse-free survival (RFS)] to a longer duration. This study reports the overall survival (OS) analysis of the three or six colon adjuvant (TOSCA) phase III study. It assessed different adjuvant chemotherapy durations in patients with resected high-risk stage II and stage III CC. TOSCA was an open-label, phase III, multicentre, non-inferiority trial conducted in 130 Italian centres. Patients were randomly assigned, in a 1 : 1 ratio, to receive 3 months of standard doses of FOLFOX/CAPOX, or 6 months of FOLFOX/CAPOX. Patients with histologically confirmed high-risk stage II and III CC were included, with RFS being the primary end point. OS was a secondary end point. From June 2007 to March 2013, 3759 patients were accrued. At a median follow-up of 7 years, the hazard ratio (HR) for RFS of the 3-month versus 6-month arms was 1.13; 95% confidence interval (CI) 0.99-1.29, P for non-inferiority = 0.380, P for superiority = 0.068, crossing the non-inferiority limit of 1.20. This result did not allow us to reject the null hypothesis of the inferiority of the 3-month arm. The HR for OS of the 3-month versus 6-month arms was 1.09 (95% CI 0.93-1.26, P for superiority = 0.288). At the last follow-up analysis, the absolute OS difference between arms was <1%. The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. The extra benefit provided by the longer treatment should be balanced against the extra toxicity of more prolonged therapy. The trial is registered with ClinicalTrials.gov , registration number: NCT0064660. • TOSCA trial compared 3 or 6 months of adjuvant chemotherapy. • We here provided the updated results of OS at 7 years of median follow up. • The HR for OS of the 3-month versus 6-month arms was 1.09 (95% CI 0.93-1.26, P for superiority = 0.288). • At the last follow-up analysis, the absolute OS difference between arms was <1%. • The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. [ABSTRACT FROM AUTHOR]

Background and Aim: As the significance of the quantitative fecal immunochemical test (FIT) in patients who previously underwent a colonoscopy is unknown, this study aimed at investigating the association between fecal hemoglobin concentration and the risk of colorectal cancer (CRC). Methods and Results: We retrospectively analyzed FIT‐positive patients who underwent a colonoscopy through our opportunistic annual screening program from April 2010 to March 2017 at the Kyoto Second Red Cross Hospital. We stratified them into no colonoscopy and past colonoscopy (>5 years or ≤5 years) groups based on whether they had a history of undergoing a colonoscopy and analyzed the correlation between fecal hemoglobin concentration and advanced neoplasia or invasive cancer detection in each group. We analyzed 1248 patients with positive FIT results. There were 748 (59.9%), 198 (15.9%), and 302 (24.2%) patients in the no colonoscopy, past colonoscopy (>5 years), and past colonoscopy (≤5 years) groups, respectively. In the no colonoscopy group, the advanced neoplasia detection rate significantly increased with the fecal hemoglobin concentration (P < 0.001). However, no significant trend was observed in the past colonoscopy (both >5 years and ≤5 years) group (P = 0.982). No invasive cancer was detected in the past colonoscopy (≤5 years) group. Conclusion: The risk of CRC might be low even if fecal hemoglobin concentration was high, especially in those who underwent colonoscopy within 5 years. [ABSTRACT FROM AUTHOR]

Background Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided. Results Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; P het =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; P het =.01) tumors. Conclusions We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors. [ABSTRACT FROM AUTHOR]

The Controlling Nutritional Status (CONUT) score is a marker of nutrition and is associated with poor survival in various kinds of cancers. However, no reports have yet compared risk factors for colorectal cancer recurrence using a nutritional index. We assessed the predictive value of the CONUT score compared with the modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) in colorectal cancer (CRC) patients. We performed a retrospective cohort study of the medical records of 336 consecutive patients with stage I-I I I CRC who underwent curative resection at a single institution in 2012–2017. Univariate and multivariate analyses were conducted to identify prognostic factors associated with relapse-free survival (RFS) and overall survival (OS). The low CONUT score group exhibited higher RFS and longer OS compared to the high CONUT score group (82.2% vs. 63.3%, p = 0.002 and 95.5% and 86.2%, p = 0.005, respectively). The Akaike's information criterion values of each index for RFS and OS were superior in CONUT score (723.71 and 315.46, respectively) compared to those of PNI (726.95 and 316.52) and mGPS (728.15 and 318.07, respectively). The CONUT score was found to be a good predictor of RFS and OS in patients with resectable CRC. [ABSTRACT FROM AUTHOR]

Aim: With population aging, the number of frail patients with colorectal cancer has increased. The Clinical Frailty Scale (CFS) is a validated tool for assessing frailty, and higher scores indicate worse clinical outcomes following cardiovascular procedures. This retrospective study aimed to examine preoperative frailty in relation to recurrence and mortality following curative resection of colorectal cancer. Methods: We retrospectively analyzed data for 729 consecutive patients undergoing curative resection of stage I–stage III colon and rectal adenocarcinoma between January 2009 and December 2016. Frailty was assessed using the CFS: 1 (very fit) to 9 (terminally ill), and frailty was defined as CFS ≥ 4. Recurrence‐free survival (RFS) and overall survival (OS) were compared between frail and nonfrail patients. Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. Results: CFS score was negatively correlated with the Barthel index of activities of daily living (Spearman's ρ = −0.83). Of the 729 patients, 253 (35%) were frail. In multivariable analyses adjusting for potential confounders including age and disease stage, frailty was independently associated with shorter RFS (multivariable HR: 1.70, 95% confidence interval: 1.25‐2.31, P <.001) and OS (multivariable HR: 2.04, 95% confidence interval: 1.40‐2.99, P <.001). There were no significant interactions of frailty with age and disease stage regarding RFS and OS (Pinteraction >.72). Conclusion: Preoperative frailty was independently associated with shorter RFS and OS following resection of nonmetastatic colorectal cancer, regardless of age and disease stage. Further trials are needed to establish treatment strategies for frail patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Aspirin has been associated with a reduced risk of colorectal cancer, and possibly of a few other digestive tract cancers. The quantification of risk reduction and the optimal dose and duration of aspirin use for the prevention of colorectal and other digestive tract cancers remains unclear. To provide an up-to-date quantification of this association, we conducted a systematic review and meta-analysis of all observational studies on aspirin and cancers of the digestive tract sites published through March 2019. We estimated the pooled relative risk (RR) of cancer for regular aspirin use versus non-use using random-effects models, and, whenever data were available, we investigated the dose- and duration-risk relations. Regular aspirin use is associated with a reduced risk of colorectal cancer [RR = 0.73, 95% confidence interval (CI) = 0.69–0.78, 45 studies], squamous-cell esophageal cancer (RR = 0.67, 95% CI = 0.57–0.79, 13 studies), adenocarcinoma of the esophagus and gastric cardia (RR = 0.61, 95% CI = 0.49–0.77, 10 studies), stomach cancer (RR = 0.64, 95% CI = 0.51–0.82, 14 studies), hepato-biliary tract cancer (RR = 0.62, 95% CI = 0.44–0.86, five studies), and pancreatic cancer (RR = 0.78, 95% CI = 0.68–0.89, 15 studies), but not of head and neck cancer (RR = 0.94, 95% CI = 0.76–1.16, 10 studies). The associations are somewhat stronger in case-control than in cohort and nested case-control studies and are characterized by some between-study heterogeneity. Risk estimates are consistent across sex, geographical areas, and other selected covariates. For colorectal cancer, an aspirin dose between 75 and 100 mg/day conveys a risk reduction of 10%, and a dose of 325 mg/day of 35%. For all neoplasms, except head and neck cancer, inverse duration-risk relations with aspirin use are found. The present comprehensive meta-analysis supports and further quantifies the inverse association between regular aspirin use and the risk of colorectal and other digestive tract cancers, including some rare ones. The favorable effect of aspirin increases with longer duration of use, and, for colorectal cancer, with increasing dose. • Forty-five studies on over 150 000 colorectal cancers indicate that aspirin use is associated with a greater than 25% risk reduction. • Colorectal cancer risk is inversely related to the dose and duration of aspirin use. • Aspirin use is also inversely related to esophageal, stomach, liver, and pancreatic cancer. [ABSTRACT FROM AUTHOR]

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Body fatness increases the risk of colorectal cancer (CRC). Insulin resistance and altered adipokines are potential mechanisms, but previous biomarker studies have been inconsistent. Intertumoral heterogeneity might provide an explanation. We investigated insulin, C-peptide, adiponectin, and leptin in relation to CRC molecular subtypes using a nested case-control design (1010 cases, 1010 matched controls, median 12.3 years from baseline to CRC diagnosis) from the population-based Northern Sweden Health and Disease Study. Repeated samples were available from 518 participants. Risks of CRC and subtypes, defined by tumor BRAF and KRAS mutations and microsatellite instability (MSI) status, were estimated using conditional logistic regression and linear mixed models. Higher C-peptide and lower adiponectin were associated with increased CRC risk (odds ratios per standard deviation increase (95% CI): 1.11 (1.01, 1.23) and 0.91 (0.83, 1.00), respectively), though weakened when adjusted for body mass index. Insulin and leptin were not associated with CRC risk. Within-individual time trajectories were similar in cases and controls, and no subtype-specific relationships were identified (all Pheterogeneity > 0.1). Adiponectin was weakly inversely associated with the risk of KRAS-mutated (P = 0.08) but not BRAF-mutated or KRAS/BRAF-wildtype CRC, consistent with the one previous study. These findings contribute to an increased understanding of the complex role of body size in CRC. [ABSTRACT FROM AUTHOR]

Introduction: The association between long-acting insulin analogs and colorectal cancer is uncertain, with previous studies reporting discrepant findings.Objective: To determine whether the use of long-acting insulin analogs is associated with an increased risk of colorectal cancer, when compared with use of intermediate-acting human insulins among patients with type 2 diabetes.Methods: We conducted a population-based study using the United Kingdom Clinical Practice Research Datalink (CPRD). We identified patients newly treated with either a long-acting insulin analog or an intermediate-acting human insulin between September 1, 2002 and January 31, 2018, with follow-up until January 31, 2019. Each long-acting insulin analog user was propensity score-matched to one intermediate-acting human insulin user, and a lag of 1 year was imposed. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of colorectal cancer, comparing long-acting insulin analogs with intermediate-acting human insulin. Secondary analysis was conducted to assess whether there was a duration-response relationship.Results: A total of 10,734 new long-acting insulin analog users were matched to 10,734 new intermediate-acting human insulin users. After a median follow-up of 2.8 years, the use of long-acting insulin analogs was not associated with an increased risk of colorectal cancer, compared with intermediate-acting human insulin (1.80 vs. 1.87 per 1000 person-years, respectively; HR 0.96, 95% CI 0.70-1.34). There was no evidence of a duration-response relationship.Conclusions: The results of this population-based study indicate that use of long-acting insulin analogs is not associated with an overall increased risk of colorectal cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation. [ABSTRACT FROM AUTHOR]

Background. The association between gallbladder (GB) disease and colorectal precancerous lesions remains elusive. This study sought to explore the association between GB disease and colorectal neoplasms at different locations. Methods. Patients who received general health checkup from January to December 2008 were included and subgrouped into three groups by polyp location: proximal, distal, and whole colon. GB disease and other known risk factors for colon cancer were compared and analyzed. Different types of polyps at different locations were further investigated. Results. Of a total of 3136 patients (1776 men and 1360 women; mean age, 49.3 years) who had colon polyps, 212 (6.8%) had GB stone and 512 (16.3%) had GB polyps. Patients in the proximal colon polyp group had higher rates of GB polyps and stones. GB polyps were independently associated with proximal colon polyps, including both hyperplastic polyps (odds ratio, 1.523; P=0.034) and adenomatous polyps (odds ratio, 1.351; P=0.048). No relationship between GB polyps and distal or any colon polyps was observed. Irrespective of the polyp location (i.e., proximal, distal, or any part of the colon), GB stone did not show any association with colon polyp. Conclusions. We suggested that GB polyps are associated with proximal colon polyps. Colonoscopy may be a more effective strategy for screening proximal precancerous lesions among patients with GB polyps. The association between GB disease and colon polyps demands further prospective investigation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of PER2 and its correlation with the development of colorectal cancer. Methods:A total of 203 cases of colorectal cancer patients who underwent radical enterectomy in Shanghai General Hospital were included. By realtime PCR and immunohistochemistry, PER2 expression in the tumor tissue and adjacent normal tissue were detected, and the correlation of PER2 expression with the pathological characterstics and clinical outcome were statistically analyzed. Results: PER2 expression in tumor was significantly lower than that of the normal tissue in colorectal cancer patients(P<0.001). As compared to PER2-positive tumors,a larger proportion of colorectal cancer patients with PER2-negative tumors had distant metastases(P=0.026) and were AJCC stage IV(P=0.011). Conclusion: PER2 gene expression decrease in colorectal cancer patients, and PER2 may be helpful for AJCC staging of the patients and assessing whether they have tumor metastasis or not. [ABSTRACT FROM AUTHOR]

Globally, colorectal cancer (CRC) is a substantial public health burden, and it is increasingly affecting populations in Asian countries. The overall prevalence of CRC is reported to be low in Asia when compared with that in Western nations, yet it had the highest number of prevalent cases. This review described the prevalence of CRC in Asia according to the International Agency for Research on Cancer from World Health Organization (WHO) database and summarized its major risk factors. Nonmodifiable factors include genetic factors, ethnicity, age, gender, family history and body height; smoking, alcohol drinking, weight, Westernized diet, physical inactivity, chronic diseases and microbiota were involved in environmental factors. These risk factors were separately discussed in this review according to published literature from Asian countries. CRC screening has been playing an important role in reducing its disease burden. Some recommendations on its screening practices have been formulated in guidelines for Asia Pacific countries. [ABSTRACT FROM AUTHOR]

Purpose Both genetic and lifestyle factors contribute to the risk of colorectal cancer, but each individual factor has a limited effect. Therefore, we investigated the association between colorectal cancer and the combined effects of genetic factors or/and lifestyle risk factors. Materials and Methods In a case-control study of 632 colorectal cancer patients and 1,295 healthy controls, we quantified the genetic risk score for colorectal cancer using 13 polymorphisms. Furthermore, we determined a combined lifestyle risk score including obesity, physical activity, smoking, alcohol consumption, and dietary inflammatory index. The associations between colorectal cancer and risk score using these factors were examined using a logistic regression model. Results Higher genetic risk scores were associated with an increased risk of colorectal cancer (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.89 to 3.49 for the highest tertile vs. lowest tertile). Among the modifiable factors, previous body mass index, physical inactivity, heavy alcohol consumption, and a high inflammatory diet were associated with an increased risk of colorectal cancer. A higher lifestyle risk score was associated with an increased risk of colorectal cancer (OR, 5.82; 95% CI, 4.02 to 8.44 for the highest tertile vs. lowest tertile). This association was similar in each genetic risk category. Conclusion Adherence to a healthy lifestyle is associated with a substantially reduced risk of colorectal cancer regardless of individuals’ genetic risk. [ABSTRACT FROM AUTHOR]

>bold<>italic/italic<>/bold< Interval colorectal cancer (CRC) is largely related to a poor endoscopic performance or different biology in the development of the polyp. However, patient-related factors were less investigated for their association with interval cancer. We thus evaluated tumor and patient characteristics as predictors of interval cancer in a population from Israel. >bold<>italic/italic<>/bold< In this retrospective study, patients that were diagnosed with colon cancer in our institution and had 2 colonoscopies were included. Demographic parameters and tumor characteristics were compared between 84 cases with interval cancer, occurring 1–10 years after a negative colonoscopy, and 983 patients with primary CRC. In addition, patient-related features, including diabetes and diverticulosis, were compared between 51 patients with interval cancer after negative colonoscopy and 255 controls with no cancer and a previous negative colonoscopy. >bold<>italic/italic<>/bold< Compared to "positive" controls with primary cancer, patients with interval cancer were older (age 71.3 vs. 67.6, >italic/italic< = 0.003), had proximal tumor location (57 vs. 34%, >italic/italic< < 0.001) and non-advanced (0–2) tumor staging (78.5 vs. 64.8%, >italic/italic< = 0.014). Compared with -"negative" healthy controls, cases with interval cancer had only higher prevalence of diabetes (31 vs. 15%, >italic/italic< = 0.002). No significant differences were seen between patients with interval cancer occurring < 3 years and after 3–10 years. >bold<>italic/italic<>/bold< Patients with Interval cancer tend to be older and have diabetes. These patient groups should be more carefully or more frequently screened for pre-malignant lesions. [ABSTRACT FROM AUTHOR]

Background: New national guidance on urgent referral for investigation of colorectal cancer included faecal occult blood testing in 2015. A service evaluation of faecal immunochemical testing (FIT) and anaemia as risk stratification tools in symptomatic patients suspected of having CRC was undertaken. Methods: Postal FIT was incorporated into the colorectal cancer 2‐week wait (2WW) pathway for all patients without rectal bleeding in 2016. Patients were investigated in the 2WW pathway as normal, and outcomes of investigations were recorded prospectively. Anaemia was defined as a haemoglobin level below 120 g/l in women and 130 g/l in men. Results: FIT kits were sent to 1106 patients, with an 80·9 per cent return rate; 810 patients completed investigations and 40 colorectal cancers were diagnosed (4·9 per cent). FIT results were significantly higher in patients with anaemia (median (i.q.r.) 4·8 (0·8–34·1) versus 1·2 (0–6·4) μg Hb/g faeces in those without anaemia; P < 0·001). Some 60·4 per cent of patients (538 of 891) had a result lower than 4 μg haemoglobin (Hb) per g faeces (limit of detectability), and 69·7 per cent (621 of 891) had less than 10 μg Hb/g faeces. Some 60 per cent of patients with colorectal cancer had a FIT reading of 150 μg Hb/g faeces or more. For five colorectal cancers diagnosed in patients with a FIT value below 10 μg Hb/g faeces, there was either a palpable rectal mass or the patient was anaemic. A FIT result of more than 4 μg Hb/g faeces had 97·5 per cent sensitivity and 64·5 per cent specificity for a diagnosis of colorectal cancer. A FIT result above 4 μg Hb/g faeces and/or anaemia had a 100 per cent sensitivity and 45·3 per cent specificity for colorectal cancer diagnosis. Conclusion: FIT is most useful at the extremes of detectability; strongly positive readings predict high rates of colorectal cancer and other significant pathology, whereas very low readings in the absence of anaemia or a palpable rectal mass identify a group with very low risk. High return rates for FIT within this 2WW pathway indicate its acceptability. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to find risk factors for colon cancer progression with bioinformatics methods, and validated by clinical patients. Methods: Differentially expressed genes (DEGs) between colon cancer tissues and normal colon tissues were extracted from The Cancer Genome Atlas (TCGA) database using R software, amounted to 8,051. DEGs between pathologic stage I+II and stage III+IV amounted to 373, and were compared with DEGs of cancer/normal analyzed above to get the intersection of both. Ninety-six intersected DEGs were identified and defined as progressive DEGs of colon cancer. Then these 96 progressive DEGs were studied by Gene ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis using the DAVID database and visualizing by R software. A protein–protein interaction (PPI) network and functional modules were established using the STRING database. Further, an overall survival (OS) curve was drawn via the GEPIA website based on the CGA database and six progressive DEGs were found to be involved with OS of colon cancer patients. The Linkedomics website was used for detailed analysis of specific subsets of TNM. Results: Pregnancy specific glycoprotein (PSG), vitamin digestion, and absorption were confirmed to promote the progression of colon cancer. Furthermore, NTF4 was found to be associated with both OS and each subset of TNM; therefore, defined as a key risk factor for colon cancer progression. Further analysis of NTF4 expression using clinical data showed it acted as a key risk factor and diagnosis marker for colon cancer progression. Conclusion: NTF4 is a risk factor contributing to colon cancer progression and associated with overall survival. [ABSTRACT FROM AUTHOR]

Patients with stage III colonic adenocarcinoma have a spectrum of risk for recurrent disease, and histopathological variables that predict recurrence can help stratify patients into prognostic groups. To identify histopathological predictors of recurrence, we investigated the effect of implementation of the eighth edition of the American Joint Committee on Cancer (AJCC8) staging system definition of tumor deposits and International Tumor Budding Consensus Conference (ITBCC) criteria for tumor budding compared with other known prognostic variables in 256 resected colonic adenocarcinomas, including 150 stage III and 106 stage II tumors. In stage III colon cancer, tumor deposits and high tumor budding were the only independent histological variables that predicted disease recurrence. In a multivariable analysis in stage III colon cancer, tumor deposits and high tumor budding were associated with a 2.2- and 1.5-fold increased risk of developing disease recurrence, respectively (95% CI = 1.1-4,2, P = .02, and 95% CI = 1.1-2.1, P = .01, respectively). The negative prognostic effect of tumor deposits was most pronounced in patients with stage IIIB disease in which tumor deposits were associated with a 3.2-fold increased risk of disease recurrence (95% CI = 1.4-7.1; P = .005). Within the N1 cohort, patients with tumor deposits without concurrent positive lymph nodes (N1c) had a significantly decreased disease-free survival compared with patients with N0 tumors (P < .001) and patients with N1a/b tumors (P = .02). As independent risk factors for recurrence, tumor deposits and high tumor budding are important histopathological variables and should be included as a part of a routine comprehensive pathological risk assessment in stage III colon cancer. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is an important risk factor for the occurrence of colon cancer, and changes in expression of p53 and inflammatory factors are closely related to the pathogenesis of colon cancer. Therefore, changes in expression of p53 and inflammatory factors in UC were investigated to explore its intrinsic pathogenetic laws. The levels of inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-10 and IL-4, in peripheral blood of UC patients and healthy adults were detected via enzyme-linked immunosorbent assay, and the changes in p53 expression were analyzed via immunohistochemistry and western blotting, and the correlation of p53 expression with changes in cytokines was also analyzed. Moreover, changes in 45S preribosomal ribonucleic acid (preRNA) transcriptional activity in four kinds of cell lines exposed to IL-6 were analyzed and determined by using reverse transcription-quantitative polymerase chain reaction. Finally, the C-myc protein expression after IL-6 stimulation was analyzed and evaluated via western blot analysis. The levels of IL-6 and TNF-α in peripheral blood in the UC patient group were significantly increased compared with those in the healthy adult group (P<0.01), while the levels of IL-10 and IL-4 in peripheral blood were significantly decreased compared with those in the healthy adult group (P<0.01). The p53 expression had a significant negative correlation with IL-6. The results showed that IL-6 activated C-myc messenger RNA (mRNA) translation, thereby upregulating the ribosomal RNA (rRNA) transcription. Additionally, IL-6 stimulated the mouse double minute 2 homolog (MDM2)-mediated proteasomal degradation of p53 by reducing the availability of ribosomal protein used for MDM2 binding, thus resulting in the downregulation of p53 protein expression. The findings of the study show that, expression level of IL-6 was increased in UC patients, which regulates the downregulation of p53 expression level and plays a role in tumorigenesis through enhancing cell proliferation and inhibiting apoptosis. [ABSTRACT FROM AUTHOR]

Objectives: To determine the role of two genetic variants, (rs3804594) and (rs1801725), in calcium sensing receptor (CASR) gene with colorectal cancer (CRC) risk in patients visited King Abdulaziz University hospital (KAUH) in Jeddah, Saudi Arabia. Methods: Genomic DNA was extracted, by commercial DNA extraction kit, from whole blood of 100 CRC patients and 124 controls who visited KAUH from January 2016 to September 2016. Then genotype and allele distributions of both variants were determined by PCR-RFLP and DNA sequencing techniques. All statistical analyses were performed by unpaired t-test and P-values <0.05 were considered statistically significant. Results: Data obtained from χ² test showed that intron 4 variant in CASR gene was distributed 100% normally in the 224 participants, however, exon 7 variant showed 100% homozygous distribution in the controls; whereas, in CRC patients it was distributed equally into 50% heterozygous and 50% homozygous with no detection for wild type. Conclusion: Intron 4 variant (rs3804594) in CASR gene is not correlated to CRC risk. However, more investigations are needed to elucidate the role of CASR gene exon 7 (rs1801725) variant in CRC development as the current results are not definitive. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) within binding sites of microRNAs (miRNAs) could modify cancer susceptibility by changing the binding affinity of miRNAs on their target mRNA 3ʹ‐untranslated regions (UTRs). MicroRNA‐21 (miR‐21) is involved in the development of colorectal cancer. However, the relationship between SNPs within the binding sites of miR‐21 and colorectal cancer risk has not been widely investigated. A case‐control study including 1147 patients and 1203 controls was performed to evaluate the association of SNPs in miR‐21 binding sites and colorectal cancer risk. Dual‐luciferase reporter assays and functional assays were performed to evaluate the effects of miR‐21. The SNP rs6504593 C allele conferred an increased risk of colorectal cancer compared with the T allele in an additive model (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04‐1.36, P = 0.011). Dual‐luciferase reporter assays demonstrated that the rs6504593 T allele negatively post‐transcriptionally regulated IGF2BP1 by altering the binding affinity of miR‐21. Additionally, colorectal cancer cells transiently transfected with miR‐21 mimics promoted cell proliferation and suppressed apoptosis, whereas inhibition of miR‐21 decreased cell growth. These data suggest that the miR‐21 binding site SNP rs6504593 in the IGF2BP1 3ʹ‐UTR may alter IGF2BP1 expression and contribute to colorectal cancer risk. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population.Methods: To evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets.Results: After adjusting for age and gender, the "AA" genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05-3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03-4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13-5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04-4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01-4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs.Conclusions: This study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females. [ABSTRACT FROM AUTHOR]

Purpose: Functional variants in the peroxisome proliferator-activated receptor gamma (PPARG) and PPARG co-activator 1 (PPARGC1) family (e.g., PPARGC1A and PPARGC1B) genes were predicted to confer susceptibility to colorectal cancer (CRC). The aim of the present study was to explore the relationship between PPARG, PPARGC1A, PPARGC1B polymorphism and the risk of CRC. Patients and methods: We conducted a case-control study with 1,003 CRC cases and 1,303 controls. We selected the PPARG rs3856806 C>T, PPARGC1A rs2970847 C>T, rs8192678 C>T, rs3736265 G>A and PPARGC1B rs7732671 G>C and rs17572019 G>A SNPs to assess the relationship between PPARG, PPARGC1A, PPARGC1B their variants and risk of CRC. Results: We found that the PPARG rs3856806 C>T polymorphism increased the risk of CRC (TT vs. CC: adjusted OR, 1.59, 95% CI 1.08–2.35, P = 0.020; TT/CT vs. CC: adjusted OR, 1.26; 95% CI 1.06–1.49; P = 0.009 and TT vs. CC/CT: adjusted OR, 1.54; 95% CI 1.05–2.26; P = 0.028), even after a Bonferroni correction test. The stratified analysis revealed that the PPARG rs3856806 C>T polymorphism also increased the risk of CRC, especially in male, ≥61 years old, never smoking, never drinking, BMI ≥ 24 kg/m2, colon cancer and rectum cancer subgroups. Conclusion: Our findings highlight that the PPARG rs3856806 C>T polymorphism may increase the risk of CRC. In the future larger sample size case-control studies with a detailed functional assessment are needed to further determine the relationship of the PPARG rs3856806 C>T polymorphism with CRC risk. [ABSTRACT FROM AUTHOR]

Background: Vegetable consumption reduces colon cancer risk when fed in the initiation stage of carcinogenesis; however, the effect of vegetable consumption during the post-initiation stage has rarely been examined.Objective: We investigated the chemopreventive effects of feeding apiaceous and cruciferous vegetables on colon cancer risk in the post-initiation stage.Methods: Thirty male Wistar rats (∼5 wk, 92 g) were subcutaneously injected with 1,2-dimethylhydrazine 1 time/wk for 2 wk. One week after the last dose, rats were randomly assigned to 3 groups: the basal diet, an apiaceous vegetable-containing diet (API; 21% fresh wt/wt), or a cruciferous vegetable-containing diet (CRU; 21% fresh wt/wt). All diets contained ∼20% protein, 7% fat, and 63% digestible carbohydrate. Experimental diets were fed for 10 wk, after which colons were harvested.Results: CRU reduced aberrant crypt foci (ACF) number compared to the basal group (P = 0.014) and API (P = 0.013), whereas API decreased the proportion of dysplastic ACF relative to the basal group (P < 0.05). Both CRU and API reduced doublecortin-like kinase 1-positive marker expression relative to basal by 57.9% (P = 0.009) and 51.4% (P < 0.02). The numbers of CD44-positive ACF did not differ between the groups. We identified 14 differentially expressed microRNAs (miRNAs). Of these, expression of 6 miRNAs were greater or tended to be greater (P ≤ 0.10) in one or both vegetable-containing groups compared to the basal group. Bioinformatic analysis of these expression changes in miRNA predicted a change in WNT/β-catenin signaling, indicating downregulation of β-catenin in the vegetable-fed groups. Consistent with this bioinformatics analysis, β-catenin-accumulated ACF were decreased in CRU (93.1%, P = 0.012), but not in API (54.4%, P = 0.125), compared to the basal group.Conclusion: Both apiaceous and cruciferous vegetables, fed post-initiation, reduce colonic preneoplastic lesions as well as cancer stem cell marker expression in rats, possibly by suppressing oncogenic signaling through changes in miRNA expression. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of colorectal cancer is higher among patients with type 2 diabetes mellitus (T2D) than among patients without diabetes. Furthermore, men are at higher risk for developing colorectal cancer than women in the general population and also subsite-specific risks differ per sex. The aim was to evaluate the impact of T2D on these associations.Methods: A population-based matched cohort study was performed using data from the PHARMO Database Network. Patients with T2D were selected and matched (1:4) to diabetes free controls. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CRC and its subsites. HRs were determined per sex and adjusted for age and socioeconomic status. The ratio of distal versus proximal colon cancer was calculated for people with T2D and controls per sex and stratified by age.Results: Over 55,000 people with T2D were matched to > 215,000 diabetes free controls. Men and women with T2D were 1.3 times more likely to develop colorectal cancer compared to controls. Men with T2D were at higher risk to develop distal colon cancer (hazard ratio (95% confidence interval), 1.42 (1.08-1.88)), and women with T2D were at higher risk for developing proximal colon cancer (hazard ratio (95% confidence interval), 1.58 (1.13-2.19)). For rectal cancer, no statistically significant risk was observed for both men and women.Conclusions: Sex-specific screening strategies and prevention protocols should be considered for people with T2D. More tailored screening strategies may optimize the effectiveness of colorectal cancer screening in terms of reducing incidence and mortality. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the most common critical disease both in the developed and developing countries. Capecitabine, which has served in clinical practice at least for 10 years, is a first-line antidigestive tract cancer drug for its better efficacy, patient compliance, and lower side effects. An ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been developed and completely validated for simultaneous determination of capecitabine and its five metabolites in human plasma from colorectal cancer patients after administration of capecitabine tablet. One-step liquid-liquid extraction was successfully applied using ethyl acetate and isopropanol (19 : 1, V : V) for sample pretreatment. Chromatographic separation was achieved within 5 min based on an Atlantis T3-C18 column (3.0 µm, 2.1 × 100 mm) with gradient elution using mobile phases consisting of 0.0075% formic acid in water (pH 4) and in acetonitrile, and the flow rate was 0.3 mL/min. Linear range was approximately 20.0–5000.0 ng/mL for all analytes. Linear correlation coefficients were >0.99 for all regression curves. The intraday and interday accuracy and precision of the method were within ±15.0% and less than 15.0%, respectively. The mean recovery and matrix effect as well as stability of all the analytes ranged from 59.27% to 90.15% and from 74.84% to 114.48% as well as within ±15.0%. This simple, rapid, and sensitive method was successfully applied in 42 sparse clinical samples to verify its practicability. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer (CRC) remains the second most common cancer in women worldwide. Physical activity (PA) has been associated with reduced risk of CRC; however, this has been demonstrated more consistently in men, while results of studies in women have been largely equivocal. We aimed to further examine the relationship between PA patterns and the risk of CRC in women, using repeated measurements.Methods: We followed participants of the Norwegian Women and Cancer (NOWAC) Study - a nationally representative cohort. Baseline information was available for 79,184 women, and we used this information in addition to follow-up information collected 6-8 years later, for repeated measurement analysis. At enrollment, participants were cancer-free and aged 30-70 years, with a median age of 51 years. We used Cox proportional hazards regression to compute hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During an average of 14.6 years of follow-up and 1.16 million person-years, 885 cases of colon and 426 cases of rectal cancer were identified through linkage to the Norwegian Cancer Registry (median age at diagnosis: 65 years). We found no association between PA level and the risk of colon cancer in baseline or repeated measurements analyses when comparing women with PA level 1-2 to those with PA level 5-6 (reference) (baseline: HR = 0.90, 95% CI 0.66-1.23, p-trend = 0.76; repeated measurements: HR = 0.78, 95% CI 0.55-1.10, p-trend = 0.27). Results were the same when comparing PA level 9-10 to the reference level (baseline: HR = 0.80, 95% CI 0.56-1.12, p-trend = 0.76; repeated measurements: HR = 0.82, 95% CI 0.58-1.16, p-trend = 0.27). Similarly, we found no association between PA levels and the risk of rectal cancer.Conclusions: Women may need to look beyond PA in order to reduce their risk of CRC. [ABSTRACT FROM AUTHOR]

Background: Late-stage colorectal cancer (CRC) is associated with significantly less effective treatment and poorer survival than early-stage colorectal cancer.Objective: Identify and assess patient characteristics, demographic factors, and lifestyle factors that are associated with late-stage colorectal cancer at diagnosis.Approach: We linked two longstanding statewide, population-based registry databases: the New Hampshire Colonoscopy Registry and the New Hampshire State Cancer Registry, to assess the associations between patient characteristics and late-stage CRC diagnoses. The State Cancer Registry provided information on cancer stage and the Colonoscopy Registry provided detailed information on patient characteristics and lifestyle factors, allowing these factors to be analyzed in relation to colorectal cancer stage.Key Results: The risk of late-stage CRC diagnosis was highest among those diagnosed at a young age (< 50 years old) (OR 1.81, 95% CI 1.27-2.58). Those with Medicaid were also at increased risk, particularly < 65 years of age (OR 2.32, 95% CI 1.05-5.26). A family or personal history of polyps and/or CRC was associated with early stage at diagnosis (p = 0.014).Conclusions: Public health outreach and screening efforts should focused on patients at risk of late-stage CRC to encourage earlier diagnosis and prevention. Underserved patients have a lower rate of CRC screening and an increased risk of late-stage CRC, emphasizing the critical need to reach these populations. Further investigation of susceptibility characteristics and the effectiveness of non-invasive early screening techniques is warranted to address the late-stage CRC diagnoses in young individuals. [ABSTRACT FROM AUTHOR]

The consequence of food fiber has led to the expansion of a potential market for fiber-rich products and ingredients. Now days, research is being carried on novel resources of dietary fiber (DF), such as agronomic by-products which have traditionally been undervalued. The dietary fibers have its vital role in many physiological processes as well as in the avoidance of many ailments. However, dietary fibers have a number of scientific properties that can be applied in the formulation of foods resulting in surface modification and augmentation of the stability of the foods during their manufacturing and storage. There is a limited study on the effects of dietary fiber on vitamins. This signifies that less-fiber diets can increase the risk of ailment like colon cancer. The usage of fibers from new origins that are currently not fully exploited such as from bacteria, mosses, seaweeds, fruits and vegetables and the prospect of modifying the fibers joining them with other constituents and enhancing their nutritional and sensory attributes, would possibly broaden the field of application for dietary fibers. The present review assesses the classification, nutritional properties, physico-chemical properties and therapeutic functions of dietary fiber. The diets with the high intake of fiber are known to have positive effects on the health. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to describe the current status of aspirin use and the demographic characteristics of patients on aspirin for primary and secondary prevention of cardiovascular diseases. Methods: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) trial was a multicenter, cross-sectional, and observational study conducted in Turkey. The study was planned to include 5000 patients from 14 cities in Turkey. The data were collected at one visit, and the current clinical practice regarding aspirin use was evaluated (ClinicalTrials.gov number NCT03387384). Results: The study enrolled all consecutive patients who were admitted to the outpatient cardiology clinics from March 2018 until June 2018. Patients should be at least 18 years old, have signed written informed consent, and on aspirin (80-325 mg) therapy within the last 30 days. Cardiologists from the hospital participates in the study. Patients were divided into 2 categories according to presence or absence of atherosclerotic cardiovascular disease, namely secondary prevention group and primary prevention group, respectively. The appropriate use of aspirin in the primary and secondary prevention groups was assessed according to the European Society of Cardiology guidelines and US Preventive Services Task Force. The patients' gastrointestinal bleeding risk factors and colorectal cancer risk were evaluated. Conclusion: The ASSOS registry will be the most comprehensive and largest study in Turkey evaluating the appropriateness of aspirin use. The results of this study help understand the potential misuse of aspirin in a real-world setting. [ABSTRACT FROM AUTHOR]

Early-onset colorectal cancer (EOCRC) is defined as colorectal cancer (CRC) diagnosed before the age of 50. Alarmingly, there has been a significant increase in EOCRC diagnoses' worldwide over the past several decades. Emerging data suggest EOCRCs have distinguishing clinical, pathological, biological and molecular features; and thus, are a fundamentally different subtype of CRCs. Unfortunately, there is no simple explanation for the causes of EOCRC. Scientifically rigorous studies are needed to determine what may be driving the challenging epidemiology of EOCRC. We contend here that a reasonable hypothesis is that prenatal risk factors such as maternal stress and associated sleeping disorders influence offspring epigenetic make-up, and shape immune system and gut health contributing to an increased risk for EOCRC. [ABSTRACT FROM AUTHOR]

Cancer is a set of diseases characterized by uncontrolled cell growth. In certain cancers of the gastrointestinal tract, the adenomatous polyposis coli (APC) tumor suppressor gene is altered in either germline or somatic cells and causes formation of risk factors, such as benign colonic or intestinal neoplasia, which can progress to invasive cancer. APC is a key component of the WNT pathway, contributing to normal GI tract development, and APC alteration results in dysregulation of the pathway for production of polyamines, which are ubiquitous cations essential for cell growth. Studies with mice have identified nonsteroidal anti-inflammatory drugs (NSAIDs) and difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, as potent inhibitors of colon carcinogenesis. Moreover, gene expression profiling has uncovered that NSAIDs activate polyamine catabolism and export. Several DFMO-NSAID combination strategies are effective and safe methods for reducing risk factors in clinical trials with patients having genetic or sporadic risk of colon cancer. These strategies affect cancer stem cells, inflammation, immune surveillance, and the microbiome. Pharmacotherapies consisting of drug combinations targeting the polyamine pathway provide a complementary approach to surgery and cytotoxic cancer treatments for treating patients with cancer risk factors. In this Minireview, we discuss the role of polyamines in colon cancer and highlight the mechanisms of select pharmacoprevention agents to delay or prevent carcinogenesis in humans. [ABSTRACT FROM AUTHOR]

Abstract Orexins (orexin-A and orexin-B) are hypothalamic peptides that are produced by the same precursor and are involved in sleep/wake control, which is mediated by two G protein-coupled receptor subtypes, OX1R and OX2R. Ulcerative colitis (UC) is an inflammatory bowel disease, (IBD) which is characterized by long-lasting inflammation and ulcers that affect the colon and rectum mucosa and is known to be a significant risk factor for colon cancer development. Based on our recent studies showing that OX1R is aberrantly expressed in colon cancer, we wondered whether orexin-A could play a role in UC. Immunohistochemistry studies revealed that OX1R is highly expressed in the affected colonic epithelium of most UC patients, but not in the non-affected colonic mucosa. Injection of exogenous orexin-A specifically improved the inflammatory symptoms in the two colitis murine models. Conversely, injection of inactive orexin-A analog, OxB7–28 or OX1R specific antagonist SB-408124 did not have anti-inflammatory effect. Moreover, treatment with orexin-A in DSS-colitis induced OX1R−/− knockout mice did not have any protective effect. The orexin-A anti-inflammatory effect was due to the decreased expression of pro-inflammatory cytokines in immune cells and specifically in T-cells isolated from colonic mucosa. Moreover, orexin-A inhibited canonical NFκB activation in an immune cell line and in intestinal epithelial cell line. These results suggest that orexin-A might represent a promising alternative to current UC therapies. Highlights • OX1R is highly expressed in human colonic mucosa from UC patients. • Injection of orexin-A improves inflammation symptoms in two murine. • Orexin-A down-regulates the pro-inflammatory cytokine production by immune cells isolated from colonic mucosa. • Orexin-A inhibits IL-8 secretion in immune cell line and in intestinal epithelial cell line. [ABSTRACT FROM AUTHOR]

Abstract The lack of efficient tumor invasion and metastatic biomarkers led to high mortality rates in colon cancer patients. Aberrant expression of ubiquitin-specific protease 6 (USP6) was involved in several diseases including cancer, while its role in the progression of colon cancer was still unclear. In this study, USP6 was evaluated at both mRNA and protein levels by using RT-PCR, western blot and immunohistochemistry staining analyses. The results revealed that high USP6 expression predicted poor disease-specific survival and overall survival through Kaplan-Meier analyses with log-rank tests, univariate and multivariate Cox analyses. Furthermore, cell function assay demonstrated that USP6 could promote colon cancer cells' invasion in vitro and liver metastasis in vivo. These findings indicated that high USP6 expression contributed to the progression of colon cancer and USP6 may be a valuable prognostic factor in patients with colon cancer. Highlights • USP6 is highly expressed in colon cancer tissues at both mRNA and protein levels. • High USP6 expression was closely associated with the invasion and metastasis of colon cancer. • USP6 overexpression promotes colon cancer cell invasion and metastasis both in vitro and in vivo. • USP6 is considered as a novel gene in promoting the invasion and metastasis of colon cancer. [ABSTRACT FROM AUTHOR]

Background: There is increasing interest in using a quantitative faecal immunochemical test (FIT) to rule out colorectal cancer (CRC) in patients with high-risk symptoms in primary care.Aim: This study aimed to investigate GPs' attitudes and willingness to use a FIT over an urgent 2-week wait (2WW) referral.Design and Setting: A cross-sectional online survey involving 1024 GPs working across England.Method: Logistic regression models were used to explore the likelihood of GPs using a FIT instead of a 2WW referral, and reported using odds ratios (ORs) and 95% confidence intervals (95% CIs).Results: Just over one-third of GPs (n = 365) preferred to use a FIT as a rule-out test over a 2WW referral. GPs were more willing if they were: aged 36-45 years (OR 1.59 [95% CI = 1.04 to 2.44]); 46-55 years (OR 1.99 [95% CI = 1.14 to 3.47]); thought a FIT was highly accurate (OR 1.63 [95% CI = 1.16 to 2.29]); thought patients would benefit compared with having a colonoscopy (OR 2.02 [95% CI = 1.46 to 2.79]); and were highly confident about discussing the benefits of a FIT (OR 2.14 [95% CI = 1.46 to 3.16]). GPs were less willing if they had had >10 urgent referrals in the past year (OR 0.62 [95% CI = 0.40 to 0.94]) and thought that longer consultations would be needed (OR 0.61 [95% CI = 0.44 to 0.83]).Conclusion: The study findings suggest that the acceptability of using a FIT as a rule-out test in primary care is currently low, with less than half of GPs who perceived the test to be accurate preferring it over colonoscopy. Any potential guideline changes recommending a FIT in patients with high-risk symptoms, instead of urgent referral to rule out CRC, are likely to require intensive supporting educational outreach to increase GP confidence in the accuracy and application of a FIT in this context. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the leading cancers throughout the world. It represents the third most common cancer and the fourth in mortality. Most of CRC are sporadic, arise with no known high-penetrant genetic variation and with no previous family history. The etiology of sporadic CRC is considered to be multifactorial and arises from the interaction of genetic variants of low-penetrant genes and environmental risk factors. The most common well-studied genetic variation is single nucleotide polymorphisms (SNPs). SNP arises as a point mutation. If the frequency of the sequence variation reaches 1% or more in the population, it is referred to as polymorphism, but if it is lower than 1%, the allele is typically considered as a mutation. Lots of SNPs have been associated with CRC development and progression, for example, genes of TGF-β1 and CHI3L1 pathways. TGF-β1 is a pleiotropic cytokine with a dual role in cancer development and progression. TGF-β1 mediates its actions through canonical and noncanonical pathways. The most important negative regulatory protein for TGF-β1 activity is termed SMAD7. The production of TGF-β can be controlled by another protein called YKL-40. YKL-40 is a glycoprotein with an important role in cancer initiation and metastasis. YKL-40 is encoded by the CHI3L1 gene. The aim of the present review is to give a brief introduction of CRC, SNP, and examples of some SNPs that have been documented to be associated with CRC. We also discuss two important signaling pathways TGF-β1 and CHI3L1 that influence the incidence and progression of CRC. [ABSTRACT FROM AUTHOR]

Environmental factors may increase colon cancer (CC) risk. It has been suggested that pesticides could play a significant role in the etiology of this malignancy. As agriculture is one of the mainstays of the Brazilian economy, this country has become the largest pesticides consumer worldwide. The CC burden is also increasing in Brazil. Herein, we examined data from the Brazilian Federal Government to determine whether CC mortality and pesticide consumption may be associated. Database of the Ministry of Health provided CC mortality data in Brazil, while pesticide usage was accessed at the website of Brazilian Institute of Environment and Renewable Natural Resources. The CC mortality in the Brazilian states was calculated as standard mortality rates (SMR). All Bayesian analysis was performed using a Markov chain Monte Carlo method in WinBUGS software. We observed that CC mortality has exhibited a steady increase for more than a decade, which correlated with the amount of sold pesticides in the country. Both observations are concentrated in the Southern and the Southeast regions of Brazil. Although ecological studies like ours have methodological limitations, the current dataset suggests the possibility that pesticide exposure may be a risk factor for CC. It warrants further investigation. [ABSTRACT FROM AUTHOR]

Exosome are emerging mediators of intercellular communication. Cancer-secreted exosome has an effect on the exosome donor cells and support cancer growth and metastasis. Here, we examine the TGF-β1, a multifunctional cytokine involved in the regulation of cellular signaling pathways in human cancers, significantly contributes to upregulate miR-200b in exosome from colorectal cancer cell lines. The miR-200b enriched in exosome can be transferred into a new target cell to facilitating the colorectal cancer cells proliferation. Further studies showing that the exosomal miR-200b could directly target 3′-UTRs of p27 and RND3 resulted in knockdown of respective target proteins in recipient cells. Remarkably, the overexpression of p27/kip1 in HCT-116 cell, not RND3, resulted in effectively inhibited cell proliferation which induced by exosomal miR-200b. Moreover, animal experiment studies also confirmed a stimulating effect of exosomal miR-200b on colorectal cancer cell-derived xenografts. The expression p27/kip1 have decreased in tumors xenografts after injected with exosomal miR-200b. Our observations offer an evidence that whereby exosomal specific miRNA could amplify the proliferative element into the neighboring or distant cells to effective tumor growth. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Studies have shown that alcohol consumption is a risk factor for oral, pharyngeal, laryngeal, esophageal, liver, colon, rectal and breast cancer. It would therefore be expected that cancer prevention organizations would incorporate these facts into their public stance on the consumption of alcohol. The aims of this study were to: (1) assess how national cancer societies in developed English‐speaking countries [i.e. English‐speaking countries belonging to the Organization for Economic Co‐operation and Development (OECD)] communicate alcohol‐related cancer risk to the public and (2) compare whether these organization's advocacy of increased alcohol taxes is in line with their advocacy of tobacco tax increases to reduce cancer risk. Methods: We searched the websites of the following national cancer organizations for all statements related to the relationship between alcohol consumption and cancer risk: Cancer Council Australia, Canadian Cancer Society, Irish Cancer Society, Cancer Society New Zealand, Cancer Research UK and the American Cancer Society. A categorical system was developed to code the qualitative data for health statements, alcohol consumption recommendations, and tax policy recommendations. Websites were analyzed in March of 2017. Results: All organizations, with the exception of the American Cancer Society and Canadian Cancer Society, state that alcohol is a group 1 carcinogen and that even low‐level alcohol consumption increases risk for some cancers. Additionally, while the American Cancer Society supports increasing tobacco taxes through its cancer action network, it has not advocated for increased alcohol taxes in relation to support for tobacco tax increases. Conclusion: Analysis in 2017 of the websites for national cancer societies in Australia, Canada, Ireland, New Zealand, the United Kingdom and the United States—including Cancer Council Australia, the Canadian Cancer Society, the Irish Cancer Society, Cancer Society New Zealand, Cancer Research UK and the American Cancer Society—shows that only the American Cancer Society and Canadian Cancer Society websites fail to state that alcohol is a group 1 carcinogen and can cause cancer at low doses, and that there is no safe threshold for cancer risk. [ABSTRACT FROM AUTHOR]

Aims: Several studies suggested that promoter methylation of human mutL homolog 1 (hMLH1) was associated with the risk of colorectal cancer (CRC). However, other studies did not indicate the same results. To derive a more comprehensive estimation of the association between hMLH1 methylation and CRC risk, we conducted a meta-analysis.Materials and Methods: We searched in the PubMed, EMBASE, and WanFang Medicine databases. The strength of the associations was measured by odds ratios (ORs) with 95% confidence intervals (CIs).Results: A total of 47 studies with 4296 cases and 2827 controls were included. A statistically significant association between hMLH1 methylation and CRC risk was found (OR = 9.25; 95% CI, 5.65-15.53; P < 0.001). The heterogeneity was significant (P < 0.001). In the subgroup analysis of race, Asian and Caucasian with hMLH1 methylation had increased CRC risk (OR = 12.19; 95% CI, 7.02-23.42; P < 0.001 and OR = 6.38; 95% CI, 2.17-19.64; P < 0.001). In the subgroup analysis of sample source, only the sample from tissue showed increased CRC risk (OR = 10.46; 95% CI, 6.12-17.90; P < 0.001). The Egger's test did not find publication bias (P = 0.176).Conclusions: In conclusion, this meta-analysis suggested that hMLH1 methylation was associated with an increased CRC risk. [ABSTRACT FROM AUTHOR]