Risk Of Colorectal Cancer In Patients Research Articles

Relationship Between Aspirin Use and Site-Specific Colorectal Cancer Risk Among Individuals With Metabolic Comorbidity.

The relationship between aspirin usage and the risk of colorectal cancer (CRC) among individuals with both hypertension (HTN) and diabetes mellitus (DM) remains unclear. This study aims to explore the impact of aspirin use on the site-specific CRC risk in patients with metabolic comorbidity. A case-control study was conducted among 1,331 CRC patients and 2,771 controls recruited from the Nation Cancer Center in Korea. Multinomial logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between aspirin use, metabolic disease status, and site-specific CRC risk. Among the 4,102 participants, 1,191 individuals had neither HTN nor DM, 2,044 were diagnosed with HTN, 203 with DM, and 664 presented with HTN and DM comorbidity. An increasing number of HTN and DM was associated with an increased risk of overall CRC (HTN or DM: OR, 1.70; 95% CI, 1.39-2.07; HTN and DM: OR, 8.43; 95% CI, 6.37-11.16), while aspirin use was associated with a decreased risk of overall CRC (OR, 0.31; 95% CI, 0.21-0.46). These results remained consistent across anatomical sites. Among individuals with HTN and DM comorbidity, aspirin use notably associated with lower risk of overall CRC (OR, 0.39; 95% CI, 0.21-0.72), proximal colon (OR, 0.32; 95% CI, 0.13-0.71) and rectal cancer (OR, 0.27; 95% CI, 0.08-0.97), but not distal colon cancer (OR, 0.58; 95% CI, 0.27-1.24). This study showed that aspirin use is negatively associated with overall and site-specific CRC, even among individuals with HTN and DM comorbidity.

The Impact of Bariatric Surgery on the Incidence of Colorectal Cancer in Patients with Obesity—a Systematic Review and Meta-analysis of Registry Data

PurposeCancer and obesity represent two of the most significant global health concerns. The risk of malignancy, including colorectal cancer (CRC), increases with obesity. The aim of this study was to perform a systematic review and meta-analysis to determine the value of bariatric surgery in reducing CRC risk in patients with obesity using registry data.Materials and MethodsA systematic review and meta-analysis were performed as per PRISMA guidelines. The risk of CRC was expressed as a dichotomous variable and reported as odds ratios (OR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method. A multi-treatment comparison was performed, examining the risk reduction associated with existing bariatric surgery techniques. Analysis was performed using RevMan, R packages, and Shiny.ResultsData from 11 registries including 6,214,682 patients with obesity were analyzed. Of these, 14.0% underwent bariatric surgery (872,499/6,214,682), and 86.0% did not undergo surgery (5,432,183/6,214,682). The mean age was 49.8 years, and mean follow-up was 5.1 years. In total, 0.6% of patients who underwent bariatric surgery developed CRC (4,843/872,499), as did 1.0% of unoperated patients with obesity (54,721/5,432,183). Patients with obesity who underwent bariatric surgery were less likely to develop CRC (OR: 0.53, 95% CI: 0.36–0.77, P < 0.001, I2 = 99%). Patients with obesity undergoing gastric bypass surgery (GB) (OR: 0.513, 95% CI: 0.336–0.818) and sleeve gastrectomy (SG) (OR: 0.484, 95% CI: 0.307–0.763) were less likely to develop CRC than unoperated patients.ConclusionAt a population level, bariatric surgery is associated with reduced CRC risk in patients with obesity. GB and SG are associated with the most significant reduction in CRC risk.PROSPERO RegistrationCRD42022313280.Graphical

Evaluation of the Association of Blood Group Type with Tumor Location, Polyp Type, and Colorectal Cancer Risk: A Case-Control Study

Background: Colorectal cancer (CC) is one of the most important causes of death due to cancer in the world. The association of blood groups with CC in many races has been reported in previous studies. So far, no study has evaluated the relationship between blood group type, tumor location, and polyp type. Objectives: This study aimed at evaluating the association of the ABO blood group and CC, tumor location, and polyp type. Methods: In this case-control study, 802 subjects (401 cases and 401 controls), who underwent surgery at our medical centers between 2014 and 2021, were included. The case group was selected from the hospital records of patients with CC, and the controls were selected from non-cancer patients who were admitted to the same centers for reasons other than cancer. Patients’ demographic characteristics and clinical and pathology findings were extracted from the medical profile, and blood group information was extracted from the blood bank. Multivariate logistic regression analysis was used for the predictive variables of CC. Results: The risk of CC in patients with blood type A was significantly higher than non-A. While the risk of developing CC in patients with blood type O was significantly lower than non-O O. The risk of developing neoplastic polyps was significantly higher in patients with blood type A compared to non-A. The results of multivariate analysis showed that ABO blood type A (OR Adju: 1.66) and O (OR Adju: 0.78) and neoplastic polyp type (OR Adju: 1.36) were associated with CC. Conclusions: The results of this study showed that ABO blood group type was significantly related to CC and polyp type.

Association between regular physical activity and lower incidence of colorectal cancer in patients with diabetes mellitus: a nationwide cohort study.

The aim of this work was to investigate the association between changes in physical activity (PA) status and the development of colorectal cancer (CRC) in patients with diabetes. This nationwide population study included 1 439 152 patients with diabetes who underwent a health screening provided by the Korean National Health Insurance Service between January 2009 and December 2012 and a follow-up screening after 2 years. Based on changes in PA status, participants were categorized into four groups: remained inactive, remained active, active-to-inactive and inactive-to-active. During the median follow-up period of 5.2 years, 38 244 new cases of CRC were diagnosed. Compared with the remained inactive group, among the three other groups, the remained active group had the lowest risk of CRC [adjusted hazard ratio (aHR) 0.93; 95% CI 0.90-0.96], followed by the inactive-to-active group (aHR 0.97; 95% CI 0.94-1.00) and active-to-inactive group (aHR 0.99; 95% CI 0.96-1.02), after adjusting for confounding variables (p = 0.0007). This reduction in cancer incidence in the remained active group was observed for both rectal cancer (aHR 0.87, 95% CI 0.79-0.95) and colon cancer (aHR 0.93, 95% CI 0.90-0.97), irrespective of sex. In terms of the intensity and amount of PA, moderate intensity PA was the most effective, and a positive correlation was found between the amount of PA and the reduction in CRC incidence. Regular PA was independently associated with a decreased risk of CRC in patients with diabetes. The intensity and amount of physical activity both play a role in reducing the risk.

A novel liquid biopsy methylation-based technology and early detection of colorectal cancer in patients.

e15527 Background: Since colorectal cancer (CRC) remains as the third most common and second most deadly malignant neoplasm, accurate and non-invasive detection technologies became a promising strategy to enhance early diagnosis. Our goal is to develop a liquid biopsy test able to detect methylation-based biomarkers in circulating tumor DNA (ct-DNA) collected from CRC patients' plasma. We are currently working on a digital PCR (dPCR)-based technology focused on detecting with high sensitivity and specificity our proprietary CRC specific epigenetic biomarker panel. Methods: We developed a bioinformatic platform that identifies methylation-based biomarkers from genome-wide Illumina 450K methylation data available in GDC-TCGA public databases. The platform uses multidimensional analysis algorithms and, through a predictive model, establishes a ranking with the most appropriate diagnostic epigenetic biomarkers. First, we tested the selected biomarkers in tumor tissue and in distant colonic mucosa from average risk CRC patients using qPCR. Then, ct-DNA from plasma samples of CRC patients and circulating DNA (cf-DNA) from risk matched negative colonoscopy-confirmed healthy individuals was analyzed by a novel dPCR-based technology in order to detect our panel of epigenetic biomarkers. Lastly, we applied a ROC analysis to the Area Under the Curve (AUC) values and obtained the corresponding sensitivity and specificity results. Results: Illumina 450K methylation data from primary tumor and normal tissue was incorporated into our bioinformatic platform that subsequently ranked 275 candidate genes. Based on several classification criteria we selected a panel composed of the three best ranked candidates. We validated the bioinformatic platform performance in identifying sensitive and specific CRC epigenetic biomarkers by detecting the presence of these biomarkers in tumor mucosa from paired CRC patients and its absence in distant colonic mucosa (n = 20) using qPCR. Furthermore, we applied our dPCR-based technology to simultaneously detect the three-gene panel of epigenetic biomarkers in ctDNA from 34 CRC patients and cfDNA from 33 healthy individuals. We obtained an overall AUC = 0.92, with 76% sensitivity (95% CI: 60-87%) and 90.9% specificity (95% CI: 76-97%). Conclusions: We validated a technology capable of detecting a novel and proprietary methylation-based biomarkers panel. This accurate liquid biopsy technology based on epigenetic biomarker detection applies dPCR and might be implemented in screening or early colorectal cancer detection. Although our technology needs further clinical validations and optimizations, we consider that the obtained results are strong enough to evolve in a complete epigenetic biomarker's blood-based test.

AB030. SOH23ABS_142. The impact of bariatric surgery on the incidence of colorectal cancer in patients with obesity—a systematic review and meta-analysis of registry data

Background: Cancer and obesity represent two of the most significant global health concerns. The risk of malignancy, including colorectal cancer (CRC), increases with obesity. We aimed to determine the impact of bariatric surgery on CRC risk in patients with obesity using registry data.

Obstructive Sleep Apnea and Colorectal Cancer: A Systematic Review and Meta-Analysis.

Obstructive sleep apnea (OSA), characterised by recurrent episodes of upper airway collapse, intermittent hypoxia (IH) and sleep fragmentation (SF), has been associated with carcinogenesis in pre-clinical models. The relationship between OSA and colorectal cancer (CRC) in clinical studies is controversial. The objective of this meta-analysis was to assess the association between OSA and CRC. Two independent investigators searched studies indexed in CINAHL, MEDLINE, EMBASE, the Cochrane Database and clinicaltrials.gov that were randomised controlled trials (RCT) or observational studies evaluating the relationship between OSA and CRC. Studies were included if they had available odds ratios (OR) and relative risks (RR) or if hazard ratios (HR) with 95% confidence intervals (CI) were available and a reference group composed of participants who did not have OSA. OR and 95% CI were calculated using a random-effect, generic inverse variance method. We included four observational studies out of 85 records, comprising a combined cohort of 5,651,662 identified patients in the data analysis. Three studies used polysomnography to identify OSA. The pooled OR of CRC in patients with OSA was 1.49 (95% CI, 0.75 to 2.97). The statistical heterogeneity was high with I2 of 95%. Our study is unable to conclusively point towards OSA being a risk factor in the development of CRC, despite the plausible biological mechanisms for this. Further well-designed prospective RCT assessing the risk of CRC in patients with OSA and the impact of OSA treatments on the incidence and prognosis of CRC are needed.

Impact of changing diagnostic criteria on the diagnosis of serrated polyposis syndrome

Background and study aims The World Health Organization criteria for serrated polyposis syndrome (SPS) were established in 2010 and modified in 2019. Neither set of criteria have been validated against genetic markers or proven to be the optimal criteria for defining colorectal cancer risk in patients with serrated colorectal lesions. In this study, we sought to gain insight into how frequently the change in SPS criteria in 2019 impacted the diagnosis of SPS. Patients and methods We reviewed 279 patients with SPS diagnosed between 2010 and 2019 using the 2010 criteria (n = 163) or since 2019 using the 2019 criteria (n = 116). We reviewed whether patients in each group met the diagnosis of SPS by the alternative criteria. Results Of those diagnosed using 2010 criteria, 5.5 % did not meet 2019 criteria. Of those diagnosed by 2019 criteria, 10.3 % did not meet 2010 criteria. Conclusions Most patients with SPS in our database met the diagnosis of SPS by both 2010 and 2019 criteria, with only 5 % to 10 % of patients in each cohort not meeting the alternative diagnostic criteria.

Low-dose aspirin does not lower the risk of colorectal cancer in patients with type 2 diabetes taking metformin.

Low-dose aspirin and metformin have been individually associated with a reduced risk of cancer. Whether their concurrent use in adults with type 2 diabetes mellitus (T2DM) is associated with a reduced risk of colorectal cancer (CRC) is unclear. Among individuals with T2DM taking metformin, we sought to evaluate the association between low-dose aspirin versus no aspirin and the risk of CRC. A multiple-database new-user cohort study of patients with T2DM taking metformin was conducted between 2007 and 2010 (Clinical Data Analysis and Reporting System [CDARS], Hong Kong) and 2007-2016 (The Health Improvement Network [THIN], UK). The primary outcome was incident CRC. Patients were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any cancer, death, or until 31 December 2019. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Estimates were pooled using an inverse variance random effects model, and heterogeneity was assessed using I2 . After one-to-one propensity-score matching, 57,534 patients were included (CDARS=16,276; THIN=41,258). The median (IQR) follow-up was 9.3 (6.5-10.7) years in CDARS and 3.2 (1.1-5.8) years in THIN. The concurrent use of low-dose aspirin and metformin was not associated with a lower risk of CRC compared to metformin only (HR=0.89, 95% CI 0.75-1.05, I2 =0%). Low-dose aspirin was not associated with a lower risk of CRC in patients with T2DM taking metformin. Our study does not support the routine use of low-dose aspirin in this population.

Tissue-dependent transcriptional and bacterial associations in primary sclerosing cholangitis-associated inflammatory bowel disease.

Background: Patients with primary sclerosing cholangitis (PSC) frequently have co-ocurring ulcerative colitis (UC) and develop colorectal cancer. Colorectal cancer risk in patients with PSC-associated ulcerative colitis (PSC/UC) is elevated relative to patients with ulcerative colitis (UC) alone, reasons for which remain obscure. Understanding the molecular and microbial basis for differences between these two patient groups and how these vary across intestinal sites is important for the development of therapies to prevent colorectal cancer development in at-risk individuals. Methods: We employed ribonucleic acid sequencing (RNA-seq) analysis of biopsy samples across three intestinal tissue locations (ileum, caecum and rectum) in patients with PSC/UC (ileum n = 7, caecum n = 7, rectum n = 7), UC (ileum n = 9, caecum n = 10, rectum n = 10) and healthy controls (ileum n = 11, caecum n = 9, rectum n = 12) to determine tissue-dependent transcriptional alterations in PSC/UC. We also performed 16S ribosomal RNA (rRNA) amplicon sequencing to determine bacterial associations with PSC/UC. Results: Tissue-defining transcriptional signatures revealed that the ileum was enriched for genes involved in lipid and drug metabolism, the caecum for activated immune cells and the rectum for enteric neurogenesis. Transcriptional alterations relative to healthy control samples were largely shared between patients with PSC/UC or UC although were distinct across tissue locations. Nevertheless, we observed reduced expression of gamma-glutamyl transferase 1 ( GGT1) specifically in the ileum and caecum of patients with PSC/UC. Analysis of the bacterial component of the microbiome revealed high inter-individual variability of microbiome composition and little evidence for tissue-dependency. We observed a reduction in Parabacteroides relative abundance in the rectum of patients with PSC/UC. Conclusions: The role of gamma-glutamyl transferase in maintaining the redox environment through the glutathione salvage pathway makes our observed alterations a potential pathway to PSC-associated colorectal cancer.

Liver Cirrhosis Increases the Risk of Developing Advanced Colon Polyps.

To analyze our experience with adenoma detection rates in patients with liver cirrhosis in a community setting. Colorectal cancer (CRC) is the third most common cancer and leading cause of cancer death in men and women in the USA. The majority of CRCs arise from premalignant polyps (adenomas), which are typically detected and removed during colonoscopy. Data are limited on the risk of CRC in patients with various chronic liver diseases and the association between CRC and demographics, liver disease etiology and colonoscopy findings. A total of 351 colonoscopies were performed (2006 to 2019) in patients with liver cirrhosis. Mean age was 62.3 ± 9.4years, there were 158 females and 193 males. Adenomas were found in 159 procedures (49.07%) and were more likely found in the right colon (76.73%) vs the left colon (18.87%). Left-sided adenoma occurrence was significantly lower in women (61% lower than men, p = 0.05). Neither indication for the procedure (p = 0.08) nor advancing age (p = 0.94) affected adenoma detection rates. No significant differences were observed in the findings of adenomas between different chronic liver diseases. Adenoma detection rates in patients with cirrhosis (49%) undergoing elective colonoscopy were higher than rates reported in the literature for LT candidates (22-42%) undergoing standardized screenings. Colonoscopy screenings should be expanded to all patients with cirrhosis, regardless of etiology.

Genetic Profiling of Colorectal Carcinomas of Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease.

BackgroundPatients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) run a 10-fold increased risk of developing colorectal cancer (CRC) compared to patients with IBD only. The aim of this study was to perform an extensive screen of known carcinogenic genomic alterations in patients with PSC-IBD, and to investigate whether such changes occur already in nondysplastic mucosa.MethodsArchival cancer tissue and nondysplastic mucosa from resection specimens of 19 patients with PSC-IBD-CRC were characterized, determining DNA copy-number variations, microsatellite instability (MSI), mutations on 48 cancer genes, and CpG island methylator phenotype (CIMP). Genetic profiles were compared with 2 published cohorts of IBD-associated CRC (IBD-CRC; n = 11) and sporadic CRC (s-CRC; n = 100).ResultsPatterns of chromosomal aberrations in PSC-IBD-CRC were similar to those observed in IBD-CRC and s-CRC, MSI occurred only once. Mutation frequencies were comparable between the groups, except for mutations in KRAS, which were less frequent in PSC-IBD-CRC (5%) versus IBD-CRC (38%) and s-CRC (31%; P = .034), and in APC, which were less frequent in PSC-IBD-CRC (5%) and IBD-CRC (0%) versus s-CRC (50%; P < .001). Cases of PSC-IBD-CRC were frequently CIMP positive (44%), at similar levels to cases of s-CRC (34%; P = .574) but less frequent than in cases with IBD-CRC (90%; P = .037). Similar copy number aberrations and mutations were present in matched cancers and adjacent mucosa in 5/15 and 7/11 patients, respectively.ConclusionsThe excess risk of CRC in patients with PSC-IBD was not explained by copy number aberrations, mutations, MSI, nor CIMP status, in cancer tissue, nor in adjacent mucosa. These findings set the stage for further exome-wide and epigenetic studies.

1001. Chronic Colonization with Toxigenic Clostridioides difficile Strains Drives Colonic Tumorigenesis in Mice

BackgroundLong-term effects of chronic and/or recurrent C. difficile infections (CDI) are not well understood, and any potential role of CDI in colorectal cancer (CRC) risk is presently unknown. While pursuing efforts to identify novel procarcinogenic microbes, we identified two mucosal slurries from CRC patients (3728T and 3752T) that were tumorigenic in germ-free (GF) ApcMin/+ mice. Surprisingly, both of these CRC patient slurries were positive for C. difficile by 16S rRNA amplicon sequencing. Given the ability of other chronic infections to promote tumorigenesis (e.g., H. pylori), we hypothesized that chronic colonization with C. difficile could promote tumorigenesis in the colon. MethodsA consortium of 30 bacterial isolates including a toxigenic tcdA+ tcdB+ C. difficile strain (CIm_3728T) was cultured from GF ApcMin/+ mice gavaged with the 3728T slurry. This consortium was gavaged into additional GF ApcMin/+ mice with or without C. difficile strains CIm_3728T, CIm_3752T (isolated from mice gavaged with the 3752T slurry), or isogenic tcdA/tcdB mutants of the M7404 R027 strain. Single cell RNA sequencing (scRNAseq), high dimensional (HD) flow cytometry, and fluorescence in situ hybridization (FISH) with EUB338 and Cd198 probes were performed on distal colons from mice gavaged with either complex CRC slurries or the 3728T isolates with CIm_3728T.Results C. difficile strains drove tumorigenesis of the 3728T isolate mixture (Fig. 1A,B). Tumorigenesis was associated with early procarcinogenic signaling and spatial changes including induction of Wnt signaling in colonic epithelial progenitor cells by scRNAseq, IL-17 induction in immune cells by HD flow cytometry, and bacterial biofilm invasion deep into epithelial crypts by FISH. Tumorigenesis correlated with chronic colonization with toxigenic strains of C. difficile and was toxin-dependent, as toxin mutant strains (M7404 tcdA-tcdB-) did not induce tumors.Figure 1. C. difficile strains from CRC patients induce distal colonic tumorigenesis in germ-free (GF) ApcMin/+ mice. A consortium of 30 bacteria, including C. difficile, were isolated from mice gavaged with the 3728T human CRC mucosal slurry. These isolates were then gavaged into additional GF ApcMin/+ mice, with or without C. difficile isolates from mice gavaged with the 3728T slurry or 3752T slurry. (A) Colonic tumor numbers in GF ApcMin/+ mice at 10 wk p.i. demonstrate that C. difficile (Cd) drives the tumorigenesis of this 30-member bacterial consortium. (B) Gross tumors can be observed in the colon of a representative mouse gavaged with the 3728T isolates with the CIm_3728T (top) or CIm_3752T (middle) strain of C. difficile but not in a mouse gavaged with the isolates lacking C. difficile (bottom).ConclusionToxigenic C. difficile strains isolated from human CRC mucosal slurries were pro-carcinogenic in mice, suggesting that C. difficile is a potential driver of CRC. Given the public health burden of C. difficile, further studies are warranted to determine whether C. difficile infections (initial, recurrent, and chronic asymptomatic) increase CRC risk in patients.Disclosures Jada Domingue, PhD, AstraZeneca (Employee) James White, PhD, Personal Genome Diagnostics (Consultant) Patricia J. Simner, PhD, Accelerate Diagnostics (Grant/Research Support)Affinity Biosensors (Grant/Research Support)BD Diagnostics (Consultant, Grant/Research Support)GeneCapture (Consultant)OpGen, Inc (Consultant, Grant/Research Support)Shionogi, Inc (Consultant) Karen C. Carroll, MD, MeMed (Scientific Research Study Investigator)Meridian Diagnostics, Inc. (Grant/Research Support)Pattern Diagnostics (Advisor or Review Panel member)Scanogen, Inc. (Advisor or Review Panel member) Karen C. Carroll, MD, Pattern Diagnostics, Inc. (Individual(s) Involved: Self): Grant/Research Support; Scanogen, Inc. (Individual(s) Involved: Self): Consultant Cynthia L. Sears, MD, Bristol Myers Squibb (Grant/Research Support)Ferring (Advisor or Review Panel member)Janssen (Grant/Research Support)

Research progress on the carcinogenesis mechanism of inflammation in ulcerative colitis: a narrative review.

In this review, we have summarized the influence of inflammation-related pathological mechanisms on the development of ulcerative colitis (UC) to colorectal cancer (CRC). UC is a chronic inflammatory bowel disease (IBD) of unknown etiology that affects the colon and rectum. Long-term inflammation of UC may greatly increase the risk of CRC, and the secretion of inflammatory factors and sustained inflammation may be key drivers of UC-associated CRC progression. Compared with the general population, the risk of CRC in patients with UC is 2.4 times higher, and the mortality rate of patients with UC is higher than that of those with sporadic CRC. The use of non-steroidal anti-inflammatory drugs can reduce the probability of UC transforming into CRC. Literatures about inflammation and UC were extensively reviewed to analyze and discuss. We believe that the mechanism of continuous inflammation that promotes cancer in UC may be the result of the mutual influence of intestinal microbes, inflammatory signals, and tissue remodeling. The invasion of intestinal microorganisms activates inflammatory signals and promotes the secretion of inflammatory factors which intensifies the remodeling of the extracellular matrix (ECM) and recruits immune cells. Eventually, a mutually engendering circuit of microbial invasion, release of inflammatory mediators, and remodeling of ECM is formed, which triggers continuous inflammation and promotes development of CRC.

Colorectal Cancer Risk in Patients with Hemorrhoids: A 10-Year Population-Based Retrospective Cohort Study.

Colorectal cancer (CRC) is a common disease and one of the leading causes of cancer deaths worldwide. This retrospective cohort study evaluated the risk of developing CRC in people with hemorrhoids. Using Taiwan’s National Health Insurance Research Database, we established three sets of retrospective study cohorts with and without hemorrhoids. The first set of cohorts were matched by sex and age, the second set of cohorts were matched by propensity score without including colonoscopies, and the third set of cohorts were matched by propensity score with colonoscopies, colorectal adenomas, and appendectomies included. In the second set of cohorts, 36,864 persons with hemorrhoids that were diagnosed from 2000 to 2010 and a comparison cohort, with the same size and matched by propensity score, were established and followed up to the end of 2011 to assess the incidence and Cox proportional regression-measured hazard ratio (HR) of CRC. The overall incidence rate of CRC was 2.39 times greater in the hemorrhoid cohort than it was in the comparison cohort (1.29 vs. 0.54 per 1000 person-years), with a multivariable model measured adjusted HR of 2.18 (95% CI = 1.78–2.67) after controlling for sex, age, and comorbidity. Further analysis on the CRC incidence rates among colorectal sites revealed higher incidence rates at the rectum and sigmoid than at other sites, with adjusted HRs 2.20 (95% CI = 1.48–3.28) and 1.79 (95% CI = 1.06–3.02), respectively. The overall incidence rates of both cohorts were similar in the first and second sets of cohorts, whereas the rate was lower in the third set of hemorrhoid cohorts than in the respective comparison cohorts, probably because of overmatching. Our findings suggest that patients with hemorrhoids were at an elevated risk of developing CRC. Colonoscopy may be strongly suggested for identifying CRC among those with hemorrhoids, especially if they have received a positive fecal occult blood test result.

Tissue-dependent transcriptional and bacterial associations in primary sclerosing cholangitis-associated inflammatory bowel disease

Background: Primary sclerosing cholangitis (PSC) is a disease of the bile duct and liver. However, patients frequently have co-morbidities including inflammatory bowel disease (IBD) and colorectal cancer. Colorectal cancer risk in patients with PSC-associated ulcerative colitis (PSC/UC) is elevated relative to patients with ulcerative colitis (UC) alone, reasons for which remain obscure. Further, clinical and immunological features, and involved intestinal sites differ between PSC/UC and UC. Understanding the molecular and microbial basis for differences in cancer risk between these two patient groups and how these differ across intestinal sites is important for the development of therapies to prevent colorectal cancer development in at-risk individuals. Methods: We employed ribonucleic acid sequencing (RNA-seq) analysis of biopsy samples across three intestinal tissue locations (ileum, caecum and rectum) in patients with PSC/UC (n = 8), UC (n = 10) and healthy controls (n = 12) to determine tissue-dependent transcriptional alterations in PSC/UC. We also performed 16S ribosomal RNA (rRNA) amplicon sequencing to determine bacterial associations with PSC/UC and host-microbiome associations. Results: Tissue-defining transcriptional signatures revealed that the ileum was enriched for genes involved in lipid and drug metabolism, the caecum for activated immune cells and the rectum for enteric neurogenesis. Transcriptional alterations relative to healthy control samples were largely shared between patients with PSC/UC or UC although were distinct across tissue locations. Nevertheless, we observed reduced expression of gamma-glutamyl transferase 1 ( GGT1) specifically in the ileum and caecum of patients with PSC/UC. Analysis of the bacterial component of the microbiome revealed high inter-individual variability of microbiome composition and little evidence for tissue-dependency. We observed a reduction in Parabacteroides relative abundance in the rectum of patients with PSC/UC. Conclusions: The role of gamma-glutamyl transferase in maintaining the redox environment through the glutathione salvage pathway makes our observed alterations a potential pathway to PSC-associated colorectal cancer.

Risk of Colorectal Cancer in Serrated Polyposis Syndrome: A Systematic Review and Meta-analysis

Serrated polyposis syndrome (SPS) is characterized by development of numerous serrated lesions throughout the colorectum and increased risk of colorectal cancer (CRC). However, SPS has been an underrecognized CRC predisposition syndrome, and the true risk of CRC in SPS, both overall and in surveillance, is not known. The aim of this systematic review and meta-analysis is to describe the risk of CRC in patients with SPS. Electronic databases were searched on March 25, 2021, for studies describing CRC risk in SPS. Random-effects meta-analysis was performed to assess pooled risk of CRC among SPS patients. Primary outcomes were risk of CRC at time of SPS diagnosis and during surveillance following diagnosis of SPS. Secondary outcomes included risk of CRC prior to diagnosis of SPS and effect of World Health Organization subtype on CRC risk. Thirty-six studies including 2788 patients with SPS were included in the analysis. Overall risk of CRC in SPS was 19.9% (95% confidence interval [CI], 15.3%-24.5%). CRC risk at the time of diagnosis was 14.7% (95% CI, 11.4%-18.8%), while risk during surveillance was 2.8% (95% CI, 1.8%-4.4%), or 7 cases per 1000 person-years. SPS patients also had a high incidence of history of CRC prior to SPS diagnosis (7.0%; 95% CI, 4.6%-11.7). Subgroup analysis did not reveal any significant differences based on World Health Organization subtype. Our meta-analysis demonstrated that patients with SPS have an elevated risk of CRC, which is highest at the time of diagnosis and suggests the importance of early SPS recognition and screening to modify CRC risk. The persistently elevated CRC risk during surveillance supports current guidelines recommending heightened surveillance protocols.

Occurrence of Colorectal Cancer and the Influence of Medical Treatment in Patients With Inflammatory Bowel Disease: A Danish Nationwide Cohort Study, 1997 to 2015.

The risk of colorectal cancer (CRC) for patients with inflammatory bowel disease (IBD) has previously been investigated with conflicting results. We aimed to investigate the incidence and risk of CRC in IBD, focusing on its modification by treatment. All patients with incident IBD (n = 35,908) recorded in the Danish National Patient Register between 1997 and 2015 (ulcerative colitis: n = 24,102; Crohn's disease: n = 9739; IBD unclassified: n = 2067) were matched to approximately 50 reference individuals (n = 1,688,877). CRC occurring after the index date was captured from the Danish Cancer Registry. Exposure to medical treatment was divided into categories including none, systemic 5-aminosalicylates, immunomodulators, and biologic treatment. The association between IBD and subsequent CRC was investigated by Cox regression and Kaplan-Meier estimates. Of the IBD patients, 330 were diagnosed with CRC, resulting in a hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.03-1.28) as compared with the reference individuals. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the HR decreased to 0.80 (95% CI, 0.71-0.92). Patients with ulcerative colitis receiving any medical treatment were at significantly higher risk of developing CRC than patients with ulcerative colitis who were not given medical treatment (HR, 1.35; 95% CI, 1.01-1.81), whereas a similar effect of medical treatment was not observed in patients with Crohn's disease or IBD unclassified. Medical treatment does not appear to affect the risk of CRC in patients with IBD. The overall risk of developing CRC is significantly increased in patients with IBD as compared with the general population. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the elevated risk disappears.

Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes.

The prevalence of colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) is increasing globally. It is rarely noticed that the incidence of CRC is higher in patients with T2DM. What needs to be mentioned is that metformin, a commonly used clinical drug for T2DM, attracts scholars’ attention because of its benefits in lowering the risk of developing CRC. Hence, we try to find the common grounds of initiation of T2DM and CRC and the reason why metformin reduces the risk of CRC in patients with T2DM. We noticed consistent changes of gut microbiota, such as elevated Bacteroides, Prevotella and Bifidobacterium and depressed Firmicutes and Lactobacillus. Furthermore, many studies in recent years have proved that the efficacy of metformin, such as improving blood glucose, depends on the gut microbiota. Coincidentally, the progression of CRC is inseparable from the contributions of gut microbiota. Therefore, we first proposed the concept of the metformin-gut microbiota–CRC (in T2DM) axis to explain the effect of metformin in reducing CRC in patients with T2DM. In this review, we elaborated the new concept and its potential clinical application value.

Narrative review of colorectal cancer risk in patients with inflammatory bowel disease

: Inflammatory bowel disease (IBD) is a complex pathology that raises the risk of developing an oncological disease, mainly with the highest risk of developing dysplasia, colorectal cancer (CRC) in patients with Ulcerative Colitis (UC) and Small-Bowel Adenocarcinoma in patients with Crohn’s disease (CD). The risk of developing these complications has decreased in recent years worldwide thanks to new treatments that achieve mucosal healing with long periods of remission and surveillance programs. The risk factors are different from those in patients with CRC in the general population. The main known factors in IBD are the extent and duration of the disease and the presence of primary sclerosing cholangitis (PSC) among others. There is evidence that genetic factor changes in the mucosa usually occur in less time than in the general population, that is why endoscopic surveillance programs have been implemented and are recommended depending on the risk factors of each patient, it is important to detect early precancerous lesions to perform timely treatment, it can be endoscopic with resection of the mucosa in early stages and visible lesions by the endoscopist, but in some cases where endoscopic treatment can’t be performed or it is not recommended surgical treatment may be performed, to prevent the development of CRC, reduce mortality and improve survival rates.