scholarly journals Absence of GNAS Mutation in Colorectal Carcinogenesis

2015 ◽  
Vol 103 (2) ◽  
pp. 209-211 ◽  
Author(s):  
Hyunsu Lee ◽  
Boo-Mi La ◽  
IlSeon Hwang ◽  
Yu-Na Kang ◽  
In-Jang Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Precancerous Lesions ◽  
Medical Center ◽  
Colorectal Carcinogenesis ◽  
Hyperplastic Polyps ◽  
Colonoscopic Polypectomy ◽  
Villous Adenomas ◽  
Gnas Mutation ◽  
Serrated Adenomas

Aims and background The incidence rate of colorectal cancer (CRC) increases every year in Korean populations. However, association between the GNAS mutation and colorectal precancerous lesions has not been studied in in Korean populations. To contribute to better understanding of colorectal carcinogenesis, we analyzed GNAS mutation in 100 cancerous and 96 precancerous colorectal lesions. Methods The records of colonoscopic polypectomy performed at Dongsan Medical Center between 1999 and 2003 were reviewed retrospectively. Precancerous lesions included 7 villous adenomas, 59 tubular adenomas, and 18 sessile serrated adenomas, and 12 hyperplastic polyps. Keimyung Human Bio-Resource Bank at Dongsan Medical Center provided 100 CRC samples. Results GNAS mutation was not found in any colorectal cancer or any precancerous colorectal lesions, including villous adenoma, which is thought to harbor the mutation. Conclusions The role of GNAS mutation might be limited in colorectal neoplasms of the Korean population.

Regulation of microRNAs in Inflammation-Associated Colorectal Cancer: A Mechanistic Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
Ilangovan Ramachandran ◽  
Sneha Krishnamoorthy ◽  
Yuvaraj Sambandam ◽  
Satish Ramalingam ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Colorectal Carcinogenesis ◽  
Model Systems ◽  
Necrosis Factor Alpha ◽  
Multi Stage ◽  
Mechanistic Approach ◽  
Tnf Α ◽  
Factor Alpha

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

scholarly journals Role of colonoscopy in colorectal cancer

2001 ◽  
Vol 56 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Sergio Eduardo Alonso Araujo ◽  
Paulo Roberto Arruda Alves ◽  
Angelita Habr-Gama
Keyword(s):  
Colorectal Cancer ◽  
Cost Effective ◽  
Risk Groups ◽  
Premalignant Lesions ◽  
Average Risk ◽  
Colonoscopic Polypectomy ◽  
Histologic Diagnosis ◽  
Improvement In Survival ◽  
Common Malignancy

Colorectal cancer (CRC) represents the third most common malignancy throughout the world. Little or no improvement in survival has been effectively achieved in the last 50 years. Extensive epidemiological and genetic data are able to identify more precisely definite risk-groups so screening and early diagnosis can be more frequently accomplished. CRC is best detected by colonoscopy, which allows sampling for histologic diagnosis. Colonoscopy is the gold standard for detection of small and premalignant lesions, although it is not cost-effective for screening average-risk population. Colonoscopic polypectomy and mucosal resection constitute curative treatment for selective cases of invasive CRC. Similarly, alternative trans-colonoscopic treatment can be offered for adequate palliation, thus avoiding surgery.

scholarly journals The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ane Sørlie Kværner ◽  
Einar Birkeland ◽  
Cecilie Bucher-Johannessen ◽  
Elina Vinberg ◽  
Jan Inge Nordby ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Gut Microbiome ◽  
Precancerous Lesions ◽  
Colorectal Carcinogenesis ◽  
Screening Tools ◽  
Screening Methods ◽  
Crc Screening ◽  
Link Type ◽  
Incidence And Mortality

Abstract Background Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. Trial registration ClinicalTrials.gov Identifier: NCT01538550.

scholarly journals The Role of Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer Risk

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1379
Author(s):  
Ippokratis Messaritakis ◽  
Asimina Koulouridi ◽  
Maria Sfakianaki ◽  
Konstantinos Vogiatzoglou ◽  
Nikolaos Gouvas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Bacillus Stearothermophilus ◽  
Receptor Gene ◽  
Stage Iv ◽  
Colorectal Carcinogenesis ◽  
Thermus Aquaticus ◽  
Vdr Gene

Vitamin D deficiency has been associated with increased colorectal cancer (CRC) incidence risk and mortality. Vitamin D mediates its action through the binding of the vitamin D receptor (VDR), and polymorphisms of the VDR might explain these inverse associations. The aim of the study was the investigation of the relevance of rs731236; Thermus aquaticus I (TaqI), rs7975232; Acetobacter pasteurianus sub. pasteurianus I (ApaI), rs2228570; Flavobacterium okeanokoites I (FokI) and rs1544410, Bacillus stearothermophilus I (BsmI) polymorphisms of the VDR gene to colorectal carcinogenesis (CRC) and progression. Peripheral blood was obtained from 397 patients with early operable stage II/III (n = 202) and stage IV (n = 195) CRC. Moreover, samples from 100 healthy donors and 40 patients with adenomatous polyps were also included as control groups. Genotyping in the samples from patients and controls was performed using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). A significant association was revealed between all four polymorphisms and cancer. Individuals with homozygous mutant (tt, aa, ff or bb) genotypes were more susceptible to the disease (p < 0.001). All of the mutant genotypes detected were also significantly associated with stage IV (p < 0.001), leading to significantly decreased survival (p < 0.001). Moreover, all four polymorphisms were significantly associated with KRAS (Kirsten ras oncogene) mutations and Toll-like receptor (TLR2, TLR4 and TLR9) genetic variants. In multivariate analysis, tt, aa and ff genotypes emerged as independent factors associated with decreased overall survival (OS) (p = 0.001, p < 0.001 and p = 0.001, respectively). The detection of higher frequencies of the VDR polymorphisms in CRC patients highlights the role of these polymorphisms in cancer development and progression.

scholarly journals Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Wanxin Liu ◽  
Ren Zhang ◽  
Rong Shu ◽  
Jinjing Yu ◽  
Huan Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Cancer Susceptibility ◽  
Precancerous Lesions ◽  
Bacterial Community Composition ◽  
Intestinal Flora ◽  
Control Group ◽  
Healthy Controls ◽  
Healthy Individuals

A lot of previous studies have recently reported that the gut microbiota influences the development of colorectal cancer (CRC) in Western countries, but the role of the gut microbiota in Chinese population must be investigated fully. The goal of this study was to determine the role of the gut microbiome in the initiation and development of CRC. We collected fecal samples of 206 Chinese individuals: 59 with polyp (group P), 54 with adenoma (group A), 51 with colorectal cancer (group CC), and 42 healthy controls (group HC).16S ribosomal RNA (rRNA) was used to compare the microbiota community structures among healthy controls, patients with polyp, and those with adenoma or colorectal cancer. Our study proved that intestinal flora, as a specific indicator, showed significant differences in its diversity and composition. Sobs, Chao, and Ace indexes of group CC were significantly lower than those of the healthy control group (CC group: Sobs, Chao, and Ace indexes were 217.3 ± 69, 4265.1 ± 80.7, and 268.6 ± 78.1, respectively; HC group: Sobs, Chao, and Ace indexes were 228.8 ± 44.4, 272.9 ± 58.6, and 271.9 ± 57.2, respectively). When compared with the healthy individuals, the species richness and diversity of intestinal flora in patients with colorectal cancer were significantly reduced: PCA and PCoA both revealed that a significant separation in bacterial community composition between the CC group and HC group (with PCA using the first two principal component scores of PC1 14.73% and PC2 10.34% of the explained variance, respectively; PCoA : PC1 = 14%, PC2 = 9%, PC3 = 6%). Wilcox tests was used to analyze differences between the two groups, it reveals that Firmicutes (P=0.000356), Fusobacteria (P=0.000001), Proteobacteria (P=0.000796), Spirochaetes (P=0.013421), Synergistetes (P=0.005642) were phyla with significantly different distributions between cases and controls. The proportion of microorganism composition is varying at different stages of colon cancer development: Bacteroidetes (52.14%) and Firmicutes (35.88%) were enriched in the healthy individuals; on the phylum level, the abundance of Bacteroidetes (52.14%-53.92%-52.46%–47.06%) and Firmicutes (35.88%-29.73%-24.27%–25.36%) is decreasing with the development of health-polyp-adenomas-CRC, and the abundance of Proteobacteria (9.33%-12.31%-16.51%–22.37%) is increasing. PCA and PCOA analysis showed there was no significant (P<0.05) difference in species similarity between precancerous and carcinogenic states. However, the composition of the microflora in patients with precancerous lesions (including patients with adenoma and polyp) was proved to have no significant disparity (P<0.05). Our study provides insights into new angles to dig out potential biomarkers in diagnosis and treatment of colorectal cancer and to provide scientific advice for a healthy lifestyle for the sake of gut microbiota.

Abstract 2201: Long-term risk of colorectal cancer in patients with sessile serrated adenomas, traditional serrated adenomas, and hyperplastic polyps

2014 ◽  
Author(s):  
John A. Baron ◽  
Rune Erichsen ◽  
Stephen J. Hamilton-Dutoit ◽  
Dale C. Snover ◽  
Emina E. Torlakovic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hyperplastic Polyps ◽  
Serrated Adenomas

Antioxidant Agents and Colorectal Carcinogenesis: Role of β-Carotene, Vitamin E and Vitamin C

1996 ◽  
Vol 82 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Giuseppe Pappalardo ◽  
Antonio Guadalaxara ◽  
Giuseppe Maiani ◽  
Giovanni Illomei ◽  
Mauro Trifero ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin E ◽  
Vitamin C ◽  
Colonic Mucosa ◽  
Genetic Alterations ◽  
Colorectal Carcinogenesis ◽  
Normal Colonic Mucosa ◽  
Antioxidant Agents ◽  
Β Carotene

In consideration of findings reported in the literature and of our study, we examined the correlation between antioxidants (β-carotene, vitamin C, vitamin E) and colorectal carcinogenesis. Although diagnostic progress has been made in the last decades, no significant improvements in death rates have been achieved in the western world. Exogenous factors might be responsible for a complex alteration process of normal colonic mucosa into adenoma and carcinoma. Free radicals and reactive oxygen metabolites, due to increased production or to reduced inactivation, following a decrease in the antioxidant burden in the mucosa, might cause damage to DNA, thereby resulting in genetic alterations. This might represent the cause of the transformation process: normal mucosa→ adenoma→ carcinoma. In a prospective study, we observed a reduction of β-carotene levels in normal colonic mucosa in patients with polyps and colorectal cancer. We also showed that β-carotene supplementation raises levels of this micronutrient in the colonic mucosa of these patients. Findings from the literature and our trials show a significant decrease in the antioxidant capacity of colorectal mucosa in patients affected by colorectal cancer, although there is a significant interindividual variability. Such results suggest a possible chemopreventive role of antioxidant agents in colorectal cancer.

scholarly journals Metformin and Probiotics in the Crosstalk between Colitis-Associated Colorectal Cancer and Diabetes in Mice

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1857
Author(s):  
Sahar Al Kattar ◽  
Rosalyn Jurjus ◽  
Aline Pinon ◽  
David Yannick Leger ◽  
Abdo Jurjus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Process ◽  
Colorectal Carcinogenesis ◽  
Treatment Modalities ◽  
Downstream Signaling ◽  
Diabetes In Mice ◽  
Tnf Α ◽  
Shed Light

The co-occurrence of colorectal cancer (CRC) and diabetes mellitus along with inflammation and dismicrobism has been frequently reported. Several studies shed light on the antioncogenic potential of metformin on colorectal carcinogenesis. This study aimed to demonstrate that metformin in association with probiotics acts in a synergic effect in breaking the crosstalk, thus inhibiting CRC progression, improving diabetes, and reducing inflammation. Ninety-six male Balb/c mice, 6–8 weeks old, were divided into 16 control and experimental groups to assess the effect of the different treatments and combinations at the clinical, histological, and molecular levels. Metformin and probiotics showed beneficial outcomes on CRC and diabetes, alone and most importantly in combination. Their effects were exerted by inhibiting the inflammatory process whereby a downregulation of IL-6 and TNF-α as well as oxidative stress were depicted. The characterization of the effects of probiotics and metformin on CRC and diabetes sheds light on the role of inflammation and microbiota in this crosstalk. Deciphering the downstream signaling pathways elicited by these compounds will help in developing new effective targeted treatment modalities.

scholarly journals Human Papillomaviruses and Epstein–Barr Virus Interactions in Colorectal Cancer: A Brief Review

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 300 ◽  
Author(s):  
Queenie Fernandes ◽  
Ishita Gupta ◽  
Semir Vranic ◽  
Ala-Eddin Al Moustafa
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Cancer Progression ◽  
Epstein Barr Virus ◽  
Human Papillomaviruses ◽  
Colorectal Carcinogenesis ◽  
Mesenchymal Transition ◽  
Barr Virus ◽  
Epstein Barr

Human papillomaviruses (HPVs) and the Epstein–Barr virus (EBV) are the most common oncoviruses, contributing to approximately 10%–15% of all malignancies. Oncoproteins of high-risk HPVs (E5 and E6/E7), as well as EBV (LMP1, LMP2A and EBNA1), play a principal role in the onset and progression of several human carcinomas, including head and neck, cervical and colorectal. Oncoproteins of high-risk HPVs and EBV can cooperate to initiate and/or enhance epithelial-mesenchymal transition (EMT) events, which represents one of the hallmarks of cancer progression and metastasis. Although the role of these oncoviruses in several cancers is well established, their role in the pathogenesis of colorectal cancer is still nascent. This review presents an overview of the most recent advances related to the presence and role of high-risk HPVs and EBV in colorectal cancer, with an emphasis on their cooperation in colorectal carcinogenesis.

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