Colorectal Cancer Research Articles

Vascular endothelial growth factor pathway’s influence on bevacizumab efficacy in metastatic colorectal cancer treatment

Vascular endothelial growth factor pathway’s influence on bevacizumab efficacy in metastatic colorectal cancer treatment

The Role of Age in Predictive Models for Colorectal Cancer Risk: Insights From a Community-Based Real-World Study

The Role of Age in Predictive Models for Colorectal Cancer Risk: Insights From a Community-Based Real-World Study

Impact and mechanism study of dioscin on biological characteristics of colorectal cancer cells

Impact and mechanism study of dioscin on biological characteristics of colorectal cancer cells

Candidate genetic loci modifying the colorectal cancer risk caused by lifestyle risk factors

Objective: 65-70% of colorectal cancer (CRC) cases are considered sporadic; they arise under the influence of environmental factors in individuals lacking a family history of CRC. Low-risk genetic variants are believed to contribute to CRC risk, in tandem with lifestyle factors. Design: 616 non-familial Swedish CRC cases with at least 1 of the following five risk factors: smoking, excessive alcohol consumption, physical inactivity, adherence to an unhealthy diet, and excess body weight were included in this study. A control group consisting of 1642 healthy individuals was used. Cases and controls were genotyped from blood samples at the Centre for Inherited Disease Research at Johns Hopkins University within the Colorectal Transdisciplinary Study (CORECT) research collaboration, using the Illumina Infinium® OncoArray-500 K BeadChip. Five separate genome-wide haplotype association analyses were performed, one for each risk factor. Logistic regression models were employed to estimate associations between haplotypes (exposure) and CRC (outcome) in cases with lifestyle risk factors versus controls. Haplotypes with an odds ratio (OR) >1 were considered candidate risk markers, denoting an area of interest in the genome. A significance threshold of p < 5×10-8 was used. Results: We found 17 haplotype regions significantly associated with CRC in cases vs controls. Several regions included genes linked to inflammation and tumor promotion. Conclusion: We concluded that having certain genetic variants was associated with an increased risk of CRC compared to healthy controls among cases with known lifestyle risk factors. The interplay of lifestyle and genetic risk factors calls for further elucidation.

Abstract B022: Characterizing invasiveness in CCCR cells: Role of miR-100, miR-125b and EVs

Abstract Introduction: Extracellular vesicles have been found to be important regulators of intercellular communication between cancer cells. EV cargo varies greatly between different cell types, the composition of which provides important insights into the role of donor and recipient cells. Cetuximab Resistant Colorectal Cancer (CCCR) cells upregulate miR-100 and miR-125b and select them as cargo for their respective secreted EVs. These miRNAs are responsible for altered gene expression in the CCCR cells and can also be functionally transferred as part of EVs between donor and recipient cells. Bioinformatic analysis identified Cingulin (CGN) mRNA as one of the possible targets of miR-100 and miR-125b. The action of miRNAs leads to degradation of CGN mRNA ultimately decreasing cellular concentration of the functional protein. Absence of CGN has been associated with increased invasiveness and metastatic potential in the cancer cells. We carried out immunofluorescent imaging of CCCR cells which revealed downregulation of CGN in CCCR cells compared to the parental Cetuximab sensitive Colorectal Cancer (CC) cells. Similar effects were observed in recipient cells that obtained the miRNAs as part of EVs originating from CCCR donor cells. This project helps elucidate the roles of miR-100 and miR-125b in CCCR cells and how EVs facilitate their functional transfer between nearby cancer cells. Methods: CCCR cell lines were derived from parental CC cells in the lab of Dr. Robert Coffey by iterative selection of cetuximab resistance after growth in 3D. CRISPR/Cas9 technology was used to knockout miR-100 and miR-125b in CCCR cells. Transwell co-culture experiments were carried out to analyze EV transfer of miRNAs. Transfer was monitored by immunofluorescence using antibodies against CGN. Cells were stained and imaged as Z stacks under the 63x Immersion setting. ImageJ was used to analyze the stacks and CGN concentrations between the cells. For quantification of immunofluorescence, additional Z stack images were obtained from an inverted microscope and fluorescence digital camera. Images were analyzed using Fiji software to obtain specific CGN concentrations between the cells. Results and Discussion: Immunofluorescent imaging revealed statistically significant downregulation of CGN in CCCR cells. The protein was also downregulated in the recipient knockout cells as part of the Transwell co-culture experiment with CCCR donor cells. CGN is a tight junction protein and its absence confers increased invasiveness in 3D growth with enhanced metastasis. Decreased CGN concentration in the miR-100 and miR-125b enriched EV recipient knockout cells is indicative of functional transfer of the two miRNAs between cancer cells. These distinctive cellular dynamics could be harnessed to develop potential cancer therapies that provide a better prognosis and limit the metastatic potential of targeted cancer cells. Citation Format: Muhammad Shameer, Hannah M Nelson, Shimian Qu, Liyu Huang, Kevin C Corn, Sydney N Chapman, Nicole L Luthcke, Sara A Schuster, Tellie D Stamaris, Lauren A Turnbull, Lucas L Guy, Xiao Liu, Danielle L Michell, Elizabeth M Semler, Kasey C Vickers, Qi Liu, Jeffrey L Franklin, Alissa M Weaver, Marjan Rafat, Robert J Coffey, James G Patton. Characterizing invasiveness in CCCR cells: Role of miR-100, miR-125b and EVs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B022.

Abstract A005: APC mutations dysregulate alternative polyadenylation in cancer

Abstract Alternative polyadenylation (APA) affects most human genes and is recurrently dysregulated in cancers. However, the mechanistic origins of this dysregulation are incompletely understood. We completed an unbiased computational analysis of molecular regulators of poly(A) site selection across The Cancer Genome Atlas and identified that colorectal adenocarcinoma is distinct from all other cancer subtypes. We linked this distinction to the frequent presence of loss-of-function APC mutations in colorectal adenocarcinoma, which were strongly associated with expression of long 3′ UTRs relative to tumors lacking APC mutations. APC knockout similarly dysregulated APA in human colon organoids, and reduced APC expression was associated with APA dysregulation in tumor types lacking APC mutations. Building on previous work that identified APC as an RNA-binding protein that preferentially binds 3′ UTRs during mouse neurogenesis, we found that APC binding is most significantly enriched just upstream of proximal poly(A) sites within 3′ UTRs. Our results suggest that APC promotes proximal poly(A) site use and that APC loss contributes to pervasive APA dysregulation in human cancers. Citation Format: Austin M Gabel, Andrea E Belliville, James D Thomas, Jose Mario B Pineda, Robert K Bradley. APC mutations dysregulate alternative polyadenylation in cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A005.

Abstract B020: The Ratio of Alternatively Spliced KRAS Isoforms Plays a Role in The Tumorigenesis of Colorectal Cancer

Abstract One of the most frequently mutated oncogenes, KRAS, has two alternatively spliced isoforms, KRAS4A(4A) and KRAS4B(4B). The isoforms differ by the inclusion or exclusion of the fourth exon, resulting in 4A or 4B respectively. They undergo different post-transcriptional modifications, indicating the non-redundant nature of the two isoforms. Studies also show spatiotemporal regulation of 4A in the gastrointestinal tract of mice during development. Although 4B is considered the major isoform, the ratio of 4A to 4B is cell-type specific. We show 4A is more abundant in colorectal cancer (CRC) cells like CaCO2 and HCT116, compared to other cancer cell lines like HeLa cells and MDA-MB-468 cells. Differential splicing analysis on existing data from flow-sorted mouse colon-crypt cells (stem-like vs. differentiated) and murine intestinal organoids of colon cancer (WT vs. tumor) shows that while differentiated colon cells and WT organoids have decreased levels of 4A, stem-like cells and tumor cells show increased levels of 4A. This supports the stem-cell theory of cancer, indicating that the dysregulation of KRAS isoforms impacts colon cell differentiation in colon crypts and could lead to CRC. Interestingly, we also found that the 3’ splice site(3’SS) of exon 4A is highly conserved. RBM39, a 3’SS recognition homolog, and SRSF1 have also been shown to play a role in KRAS splicing. We hypothesize that RBM39 regulates KRAS splicing by binding the 3’SS, and SRSF1 may play a role either by binding the pre-mRNA directly or through its interaction with RBM39. Therefore, we propose a new model for alternative splicing of KRAS. The abundance of KRAS splice variants may determine the fate of colon cell differentiation and drive CRC tumorigenesis. Citation Format: Harika Reddy Pulipelli, Dr. Klemens J. Hertel. The Ratio of Alternatively Spliced KRAS Isoforms Plays a Role in The Tumorigenesis of Colorectal Cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B020.

Abstract B008: Exploring the Dual Roles of RNAs as Oncogenic Drivers and Therapeutic Targets in Cancer: A Cross-Sectional Study

Abstract RNAs have emerged as pivotal molecules in the complex landscape of cancer biology, acting as both drivers of oncogenesis and therapeutic targets. This cross-sectional experimental design research explores the dual roles of RNAs, particularly focusing on the interplay between non-coding RNAs (ncRNAs), messenger RNAs (mRNAs), and their regulatory networks in various cancer types. The study systematically analyzes RNA expression profiles across a broad spectrum of cancer samples, employing high-throughput sequencing technologies combined with bioinformatics tools to identify key RNA species that contribute to tumorigenesis. The experimental design includes the collection of tumor and adjacent normal tissues from patients diagnosed with breast, lung, and colorectal cancers. RNA extraction and sequencing are performed to generate comprehensive expression profiles. Differential expression analysis is conducted to pinpoint RNAs that are significantly dysregulated in cancerous tissues compared to their normal counterparts. Subsequently, functional assays, including RNA interference (RNAi) and CRISPR/Cas9-mediated gene editing, are utilized to validate the oncogenic or tumor-suppressive roles of these RNAs in cancer cell lines. To further elucidate the mechanistic pathways, the study integrates data from RNA-binding protein immunoprecipitation (RIP) and crosslinking immunoprecipitation (CLIP) assays, providing insights into the RNA-protein interactions that influence cancer progression. Additionally, the research evaluates the therapeutic potential of targeting these RNAs, using small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) in preclinical cancer models. Preliminary findings highlight the significance of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) in modulating key signaling pathways involved in cell proliferation, apoptosis, and metastasis. This study underscores the importance of RNA-based diagnostics and therapeutics, paving the way for innovative treatment strategies in cancer management. Citation Format: Fathelrahman M Gameel. Exploring the Dual Roles of RNAs as Oncogenic Drivers and Therapeutic Targets in Cancer: A Cross-Sectional Study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B008.

Transportery kwasów tłuszczowych jako potencjalne markery diagnostyczne raka jelita grubego

Colorectal cancer (RJG) is one of the most frequently diagnosed malignant neoplasms: approximately 1.9 million new cases are reported annually. Notwithstanding the advent of techniques for the early detection of RJG and the introduction of novel therapeutic modalities, this disease remains the second leading cause of cancer-related mortality. The results of recent studies highlight the role of fatty acid transporters, including fatty acid translocase/cluster of differentiation 36 (FAT/CD36), fatty acid transport proteins (FATPs), and fatty acid-binding proteins (FABPs), in the pathogenesis of RJG. Changes in serum concentrations and in expression levels in tumor tissue may serve as promising biomarkers for the early diagnosis of the disease and/or the monitoring of its progression and the efficacy of its treatment. Moreover, the fatty acid carriers present a promising avenue for the development of efficacious therapies against RJG.

Machine learning-driven estimation of mutational burden highlights DNAH5 as a prognostic marker in colorectal cancer

Machine learning-driven estimation of mutational burden highlights DNAH5 as a prognostic marker in colorectal cancer

Letter to Editor Regarding Article “Biopsychosocial Late Effects After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases from Colorectal and Appendiceal Cancer: A National Prospective Cohort Study”

Letter to Editor Regarding Article “Biopsychosocial Late Effects After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases from Colorectal and Appendiceal Cancer: A National Prospective Cohort Study”

Development of an optimized protocol for generating knockout cancer cell lines using the CRISPR/Cas9 system, with emphasis on transient transfection

The clustered regularly interspaced short palindromic repeats (CRISPR) system offers cost-effectiveness, high efficiency, precision, and ease of use compared to traditional gene editing techniques. In this study, we employed findings from prestigious investigations to develop an optimized approach for generating knockout cancer cell lines using a transient transfection method. This protocol introduces a distinctive approach that follows rigorous guidelines for designing gRNA to reduce off-target effects, a major challenge in CRISPR applications. Our step-by-step instructions allow researchers, particularly those with limited laboratory equipment and funding, as well as those undertaking CRISPR projects for the first time, to generate knockout cell lines using CRISPR technology in just ten weeks. This protocol covers all needs for enhancing various yields, such as transfection efficiency, and includes leveraging robust bioinformatics tools, conducting essential assays, isolating monoclonal cells via limiting dilution, validating knockout cells, and providing comprehensive troubleshooting recommendations. Using this method, we successfully created several new generations of colorectal cancer cell lines with monoallelic and biallelic knockouts of the epithelial cell adhesion molecule (EpCAM) gene. Our method, optimized for a wide spectrum of cancer cell lines, makes CRISPR more accessible for applications in personalized and precision medicine. It expands opportunities for novel investigations into cancer mechanisms and paves the way for potential therapeutic interventions.

The Extent of Tumor in the Peritoneum and Liver Influences Outcomes After Surgery for Synchronous Liver and Peritoneal Colorectal Metastases: A Cohort Study

Abstract Purpose Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRSH) or liver resection have led to increased survival in patients with peritoneal or liver metastases of colorectal cancer. Selected patients undergo concomitant CRSH and liver resection. Differences in survival and morbidity between patients who underwent concomitant surgery, CRSH or liver resection for peritoneal and/or liver metastases were compared. Methods Patients who underwent liver resection and/or CRSH for colorectal liver and/or peritoneal metastases, 2006–2016, were included. Regression analysis was used to evaluate the associations between baseline characteristics and survival. Results Overall, 634 patients were studied. Twenty-eight patients had peritoneal and liver metastases, 121 patients had peritoneal metastases only, and 485 patients had isolated liver metastases. Median survival after concomitant treatment was 23.8 months (95% CI 12.8–43.8), after CRSH 34.5 months (95% CI 27.1–41.9), and after liver resection 54.2 months (95% CI 47.4–61.0) (p < 0.001). Increased hepatic tumor burden (HR 3.2, 95% CI 1.8–5.8) and high-volume peritoneal disease (HR 6.0, 95% CI 3.7–9.8) were associated with decreased survival in multivariate analysis. Postoperative complications according to a Clavien–Dindo score > 3a were observed in 11% in the liver resection group, 15% in the CRSH group, and 11% in the concomitant treatment group (p = 0.945). Conclusions Patients treated with concomitant surgery for liver and peritoneal metastases experienced a shorter median overall survival than patients treated for metastases at an isolated site but had a similar rate of severe postoperative complications. The extent of peritoneal spread seemed to impact survival more than the tumor burden in the liver.

Colon cancer screening programs prevent cancer

In this article we comment on the article by Agatsuma et al . Our article focuses on the use of screening for colon cancer increases the likelihood of early diagnosis of colorectal cancer compared to those presenting after symptoms develop. Patients with symptoms were more likely to have left-sided lesions with resultant hematochezia and/or changes in bowel habits. In this study almost all patients in the screen group were first screened with immunochemical fecal occult blood testing. Colonoscopy was used either if it was thought to be the more appropriate initial screening modality or if the non-invasive test was positive. The exact timing when an initial screening colonoscopy should be performed is not totally clear from this study. However, early screening for colon cancer does reduce the risk of cancer diagnosis and more advanced cancer diagnoses.

Discovery of Novel 5-Cyano-3-phenylindole-Based LSD1/HDAC Dual Inhibitors for Colorectal Cancer Treatment

Discovery of Novel 5-Cyano-3-phenylindole-Based LSD1/HDAC Dual Inhibitors for Colorectal Cancer Treatment

Assessment of the frequency and risk factors for colorectal cancer in acromegaly

Assessment of the frequency and risk factors for colorectal cancer in acromegaly

Nomograms Predicting Survival, Recurrence and Beneficiary Identification of Adjuvant Chemotherapy in Treatment-naïve Patients with Rectal Cancer who Underwent Upfront Curative Resection: A multi-institutional study

Objective: To create and validate nomograms predicting overall survival and recurrence in treatment-naïve rectal cancer (RC) patients who underwent upfront surgery. Background: Although multidisciplinary treatment is standard for locally advanced RC, understanding surgical efficacy is important for determining indications for perioperative adjuvant therapy. Methods: RC patients who underwent upfront surgery at the Japanese Society for Cancer of the Colon and Rectum institutions were analyzed. A training cohort (n = 1925) of treatment-naïve patients who underwent surgery between 2007 and 2008 was analyzed to construct prognostic models predicting postoperative survival and recurrence. Discrimination and calibration were performed using an external validation cohort (n = 2957; Japanese colorectal cancer registry, procedures in 2005–2006). Effects of adjuvant chemotherapy on survival were evaluated based on nomogram prediction and Surveillance, Epidemiology, and End Results (SEER) data (n = 10,482; upfront surgery for RC in 2010–2015). Results: In the training cohort, age predicted survival, venous invasion predicted recurrence, and sex, tumor location, histological type, preoperative carcinoembryonic antigen, invasion depth, lymphatic invasion, positive radial margin, and numbers of metastatic nodes and examined nodes predicted both. Internal and external validated Harrell’s C-index values were respectively 0.77 and 0.75 for survival and 0.75 and 0.74 for recurrence. RC patients who underwent upfront surgery in the SEER database were stratified into 3 risk levels by nomogram score. Adjuvant chemotherapy did not improve 5-year survival in low-risk patients, but did so for middle-risk (62.4% vs 76.8%) and high-risk (39.4% vs 63.5%) patients. Conclusion: These nomograms could predict survival and recurrence after upfront curative resection of RC and identify cases expected to benefit more from adjuvant chemotherapy.

Analysis of Characteristics of Bovine-Derived Non-Enterotoxigenic Bacteroides fragilis and Validation of Potential Probiotic Effects

Bacteroides fragilis is a new generation of probiotics, and its probiotic effects on humans and some animals have been verified. However, research on B. fragilis in cattle is still lacking. In this study, 24 stool samples were collected from two large-scale cattle farms in Wuzhong, Ningxia, including 12 diarrheal and 12 normal stools. A non-toxigenic Bacteroides fragilis (NTBF) was isolated and identified by 16S rRNA high-throughput sequencing and named BF-1153; genome composition and genome functional analyses were carried out to reflect the biological characteristics of the BF-1153 strain. A cluster analysis of BF-1153 was performed using Mega X to explore its genetic relationship. In addition, Cell Counting Kit-8 (CCK8) was used to determine the toxic effects of the strain on human ileocecal colorectal adenocarcinoma cell line cells (HCT-8), Madin-Darby bovine kidney cells (MDBK), and intestinal porcine epithelial cells (IPECs). The results showed that BF-1153 conformed to the biological characteristics of B. fragilis. BF-1153 had no toxic effects on HCT-8, MDBK, and IPEC. Animal experiments have shown that BF-1153 has no toxic effects on healthy SPF Kunming mice. Notably, the supernatant of BF-1153 enhanced cell activity and promoted cell growth in all three cell lines. At the same time, a cluster analysis of the isolated strains showed that the BF-1153 strain belonged to the same branch as the B. fragilis strain 23212, and B. fragilis strain 22998. The results of the animal experiments showed that BF-1153 had a certain preventive effect on diarrhea symptoms in SPF Kunming mice caused by a bovine rotavirus (BRV). In summary, the strain BF-1153 isolated in this experiment is NTBF, which has no toxic effect on MDBK, HCT-8, and IPEC, and has obvious cell growth-promoting effects, especially on MDBK. BF-1153 promotes the growth and development of SPF Kunming mice when compared with the control group. At the same time, BF-1153 alleviated the diarrhea symptoms caused by BRV in SPF Kunming mice. Therefore, BF-1153 has the potential to be a probiotic for cattle.

Abstract A045: Evaluating the potential of micronuclei DNA from erythrocytes for early detection of colorectal cancer

Abstract Background: Current development in stool- and cell-free DNA (cfDNA)-based technologies have demonstrated promising potentials in colorectal cancer (CRC) diagnosis. However, early detection of CRC and advanced adenoma (AA) remains challenging. Micronuclei (MN) are extranuclear bodies containing chromatin segments resulting from errors in DNA repair. Elevated levels of MN+ erythrocytes have been studied in genotoxicity testing and cancer diagnosis. We further performed whole-genome sequencing on purified and isolated micronuclei DNA (MN-DNA) from erythrocytes in peripheral blood using the approach (WO2021/228246 A1) we previously developed. By comparing MN-DNA from colorectal cancer (CRC) patients and healthy individuals, we identified a series of tumor-associated MN-DNA features (taMN- DNA) with significant differences in read counts and developed a classification model. Here, we established an independent cohort to clinically validate the CRC model and explore its application in early cancer diagnosis. Methods: We launched a prospective observational case- control clinical trial (NCT05875584), which was used as an independent cohort to validate taMN-DNA features in CRC and to perform a comparative analysis with quantitative fecal immunochemical test (qFIT). A total of 598 samples were enrolled in this study (585 was available, including 299 HDs, 206 AAs, and 80 CRCs). We gathered peripheral blood (1-2ml) from a training cohort of 1226 individuals, a test cohort of 309 individuals and this independent cohort of 598 individuals for the MN-DNA isolation from erythrocytes and whole-genome sequencing. Predictive models were developed using distinctive taMN-DNA features identified by genome-wide analysis from training cohort to differentiate between HD and AA or CRC. Results: The predictive CRC model built on taMN-DNA features achieved an AUC of 93% and the detection of AA achieved an AUC of 82% in this clinical validation cohort. Comparing MN-DNA with qFIT, the overall sensitivity was generally consistent (91.3% vs. 87.5%), with MN-DNA achieving 86.4% sensitivity in early-stage (stage I) CRC, significantly higher than 68.2% in qFIT. Additionally, MN-DNA showed superior sensitivity in detecting AA (71.4% vs. 18.4%), with comparable specificity (90.3% vs. 96.3%). Conclusions: Our results demonstrate that MN-DNA within erythrocytes from 1-2ml peripheral blood enable accurate detection of AA and early-stage CRC. Research sponsor: Timing Biotech. Citation Format: Yurong Jiao, Xingyun Yao, Haobo Sun, Chengcheng Liu, Xiangxing Kong, Honghao Liang, Fei Meng, Jun Li, Kefeng Ding, Xiaofei Gao. Evaluating the potential of micronuclei DNA from erythrocytes for early detection of colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A045.

Gut Bacterial Microbiome Profiles Associated with Colorectal Cancer Risk: A Narrative Review and Meta-Analysis

Objective: Recent studies have shown a potential link between the gut microbiome and colorectal cancer (CRC). A wide array of research into this topic was performed over the past decade, illustrating a keen interest in the potential causal relationship between the gut microbiome and CRC. However, the cancer research community is lacking a concise review of this kind, which aims to explore the evidence linking the human gut microbiome to the risk of developing CRC. Design: This narrative review was carried out by two independent reviewers who assessed the database outcomes from Medline and EMBASE during May 2020. A meta-analysis was undertaken to study the link between Helicobacter pylori and CRC. The meta-analysis was processed through Stata (StataCorp LLC, Lakeway Drive, College Station, Texas, USA). Results: Thirty one papers were included in this narrative review, of which 12 were included in the meta-analysis. From these papers, Fusobacterium and Bacteroides were reported most frequently as enriched in those with CRC versus the control populations. The meta-analysis showed an odds ratio of 1.49 (95% CI: 1.19–1.86), including a total of 20,001 events. This meta-analysis concluded that H. pylori infection significantly increases the risk of CRC, albeit with evidence of publication bias. Conclusion: Bacteria have been found to increase the risk of CRC; however, a definitive causal relationship cannot be concluded or excluded using case-control studies. To fully understand the potential link of the bacteria listed, alterations in research design and execution are required. The assessment found a need for a large-scale cohort study conducted over a significant period of time to thoroughly evaluate the potential relationship between gut microbiome and CRC risk.