Genetic Alterations in Colon Cancer

Ulcerative colitis or Crohn's illness patients are in danger of colon cancer due to chronic inflammation, resulting from the reaction of the immune system to bacterial disease caused by genetic alterations in the colonic mucosa. Somatic cells gain genomic changes, such as TP53 that regulates MUC2 production and APC alterations linked with 𝛽-catenin and MUC1 contribution in the slight proliferation of cells. Mathematical modeling describes developmental modifications and uses the phrases to link parameter to curves of age-dependent incidence of epidemiological cancer. By using the long-lasting investigation of IBD patients to gather the genomic estimations for increasingly exact computations of IBD-explicit developmental parameters as initiation, birth, and death. Colon cancer genetic trajectory follows the structure of the composition of functions that leads to malignancies. Models of population level can be utilized to consolidate epidemiological information and in this manner describe malignant growth advancement in a population with IBD.

Download Full-text

Abstract B52: Predictor of distinct genetic alterations in African Americans with colon cancer by genomic analysis

10.1158/1055-9965.disp-10-b52 ◽

2010 ◽

Author(s):

Hassan Ashktorab ◽

Mehdi Nouraie ◽

DuaneT Smoot ◽

Hassan Brim

Keyword(s):

Colon Cancer ◽

African Americans ◽

Genomic Analysis ◽

Genetic Alterations

Download Full-text

Hemin, a major Heme molecule, induced cellular and genetic alterations of normal colonic and colon cancer cells

Pathology - Research and Practice ◽

10.1016/j.prp.2021.153530 ◽

2021 ◽

pp. 153530

Author(s):

Sujani Madhurika Kodagoda Gamage ◽

Tracie Cheng ◽

Katherine Ting-Wei Lee ◽

Lakal Dissabandara ◽

Alfred King-Yin Lam ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Genetic Alterations ◽

Colon Cancer Cells ◽

Heme Molecule

Download Full-text

TDG Gene Polymorphisms and Their Possible Association with Colorectal Cancer: A Case Control Study

Journal of Oncology ◽

10.1155/2019/7091815 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Narasimha Reddy Parine ◽

Ibrahim O. Alanazi ◽

Jilani Purusottapatnam Shaik ◽

Sooad Aldhaian ◽

Abdulrahman M. Aljebreen ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Progression ◽

Gene Polymorphisms ◽

Cancer Susceptibility ◽

Excision Repair ◽

Regulation Of Gene Expression ◽

Genetic Alterations ◽

Increased Risk ◽

Base Excision

Genetic alterations that might lead to colorectal cancer involve essential genes including those involved in DNA repair, inclusive of base excision repair (BER). Thymine DNA glycosylase (TDG) is one of the most well characterized BER genes that catalyzes the removal of thymine moieties from G/T mismatches and is also involved in many cellular functions, such as the regulation of gene expression, transcriptional coactivation, and the control of epigenetic DNA modification. Mutation of the TDG gene is implicated in carcinogenesis. In the present study, we aimed to investigate the association between TDG gene polymorphisms and their involvement in colon cancer susceptibility. One hundred blood samples were obtained from colorectal cancer patients and healthy controls for the genotyping of seven SNPs in the TDG gene. DNA was extracted from the blood, and the polymorphic sites (SNPs) rs4135113, rs4135050, rs4135066, rs3751209, rs1866074, and rs1882018 were investigated using TaqMan genotyping. One of the six TDG SNPs was associated with an increased risk of colon cancer. The AA genotype of the TDG SNP rs4135113 increased the risk of colon cancer development by more than 3.6-fold, whereas the minor allele A increased the risk by 1.6-fold. It also showed a 5-fold higher risk in patients over the age of 57. SNP rs1866074 showed a significant protective association in CRC patients. The GA genotype of TDG rs3751209 was associated with a decreased risk in males. There is a significant relationship between TDG gene function and colorectal cancer progression.

Download Full-text

Clinicopathological and Molecular Features of Patients with Early and Late Recurrence after Curative Surgery for Colorectal Cancer

Cancers ◽

10.3390/cancers13081883 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1883

Author(s):

Yuan-Tzu Lan ◽

Shih-Ching Chang ◽

Pei-Ching Lin ◽

Chun-Chi Lin ◽

Hung-Hsin Lin ◽

...

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Colon Cancer ◽

Late Recurrence ◽

Early Recurrence ◽

Genetic Alterations ◽

Curative Surgery ◽

Molecular Features ◽

Apc Mutations ◽

Early And Late Recurrence

Background: Few reports have investigated genetic alterations between patients with early and late recurrence following curative surgery for colorectal cancer (CRC). Methods: A total of 1227 stage I–III CRC patients who underwent curative resection were included retrospectively. Among them, 236 patients had tumor recurrence: 139 had early (<2 years after surgery) and 97 had late (≥2 years after surgery) recurrence. Clinicopathological features and genetic alterations were compared between the two groups. Results: Compared to those with late recurrence, patients with early recurrence were more likely to have advanced pathological node (N) categories; tumor, node, metastasis (TNM) stages; adjuvant chemotherapy treatment; liver metastases; APC mutations; and worse five-year overall survival rates. Patients with right-sided colon cancer were more likely to develop early recurrence than were those with left-sided colon cancer or rectal cancer. Regarding rectal cancer, patients with early recurrence were more likely to be at advanced pathological N categories and TNM stages than those with late recurrence. Multivariate analysis revealed old age, early recurrence, multiple-site recurrence, and BRAF and NRAS mutations to be independent prognostic factors. Conclusion: CRC patients with early recurrence have a worse OS rate and more APC mutations than those with late recurrence.

Download Full-text

Genetic testing and surgeon decision

Acta chirurgica iugoslavica ◽

10.2298/aci0402057g ◽

2004 ◽

Vol 51 (2) ◽

pp. 57-60

Author(s):

G. Guanti

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Monoclonal Antibodies ◽

Genetic Testing ◽

Clinical Outcome ◽

Locally Advanced ◽

Genetic Alterations ◽

Advanced Colon Cancer ◽

Therapeutic Decisions ◽

Staging Systems

Colorectal cancer is a highly treatable and often curable disease when localized to the bowel. Traditional pathological staging systems have been useful in predicting the outcome of colorectal cancer, but is now evident that colorectal cancer is heterogeneous and its natural story strongly correlates with genetic alterations that occur during progression from adenoma to carcinoma to metastatic disease. The goal of many studies is to define a marker, or set of markers, on which therapeutic decisions could be made with greater precision for given individuals. In investigations in which at least 100 patients with locally advanced colon cancer have been studied, those in which monoclonal antibodies to p53 (PAB 1801/DO-7/D0-1) were used have generally demonstrated that mutant or overexpression of p53 is associated with a worse clinical outcome.

Download Full-text

Design, optimization and validation of genes commonly used in expression studies on DMH/AOM rat colon carcinogenesis model

10.1101/365353 ◽

2018 ◽

Author(s):

David Bars-Cortina ◽

Antoni Riera ◽

Gemma Gou ◽

Carme Piñol-Felis ◽

Maria-José Motilva

Keyword(s):

Colon Cancer ◽

Rat Model ◽

Reference Genes ◽

Pathological Condition ◽

Melting Curve ◽

Genetic Alterations ◽

Rat Colon ◽

Published Data ◽

Quantitative Real Time Pcr ◽

Expression Studies

AbstractColorectal cancer (CRC), also known as colon cancer, is the third most common form of cancer worldwide in men and the second in women and is characterized by several genetic alterations, among them the expression of several genes. 1,2-dimethylhydrazine (DMH) and its metabolite azoxymethane (AOM) are procarcinogens commonly used to induce colon cancer in rats (DMH/AOM rat model). This rat model has been used to study changes in mRNA expression in genes involved in this pathological condition. However, a lack of proper detailed PCR primer design in the literature limits the reproducibility of the published data.The present study aims to design, optimize and validate the qPCR, in accordance with the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines, for seventeen genes commonly used in the DMH/AOM rat model of CRC (Apc, Aurka, Bax, Bcl2, β-catenin, Ccnd1, Cdnk-1A, Cox2, Gsk3beta, IL-33, iNOs, Nrf2, p53, RelA, Smad4, Tnfa and Vegfa) and two reference genes (Actb or β-actin and B2m). The specificity of all primer pairs was empirically validated on agarose gel, and furthermore, the melting curve inspection was checked as was their efficiency (%) ranging from 90 to 110 with a correlation coefficient of r2 > 0.980. Finally, a pilot study was performed to compare the robustness of two candidate reference genes.

Download Full-text

Current Understanding of Epigenetics Driven Therapeutic Strategies in Colorectal Cancer Management

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530321666210219155544 ◽

2021 ◽

Vol 21 ◽

Author(s):

Dikshita Deka ◽

Marco Scarpa ◽

Alakesh Das ◽

Surajit Pathak ◽

Antara Banerjee

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Tumor Suppressor ◽

Epithelial Cells ◽

Tumor Suppressor Genes ◽

Genetic Alterations ◽

Primary Role ◽

Suppressor Genes ◽

Cancer Management ◽

Cancer Pathogenesis

: Colorectal cancer is known to be the paramount reason for cancer deaths around the globe. It occurs due to the aggregation of epigenetic and genetic alterations in colon epithelial cells that transmute them into adenocarcinomas. Epigenetic mechanisms are interpreted as the changes in expression of the gene which is not associated with the alterations in the principal DNA sequence, while genetic changes involve modifications in oncogenes and tumor suppressor genes. The changes in the epigenetic in colon cancer that transmute colonic epithelial cells include chromatin modifications, microRNA expression, telomere length, and DNA methylation. DNA hypermethylation causes down-regulation and unsuitable expression of specific microRNA which can behave like tumor suppressor genes. Histone modifications can also influence the chromatin remodeling and the gene expression, hence performs an eminent function in silencing of the gene in colon cancer. Moreover, the telomere/telomerase interaction is a prime mechanism to embrace both cellular replicative potential and genomic instability and its malfunction plays a primary role in colon cancer. Deducing the genesis and the function of epigenetic abnormality in colon cancer pathogenesis will head to a potent prevention and therapeutic approach for colon cancer patients. Epigenetic drugs which emphasizes the convertible essence of epigenetic occurrences have accompanied the probability of epigenetic approach as a treatment alternative in colon cancer. Hence, this review is undertaken to critically envelop the recent advance events in colorectal cancer therapies with a special emphasis on remedies targeting epigenetic modulators and future challenges towards therapeutic interventions.

Download Full-text