Colorectal cancer (CRC) is the third most common cancer in the world and the second leading cause of cancer related deaths in the United States. Globally, the incidence of CRC varies widely with higher incidence rates in North America, Australia and Northern and Western Europe (Aljebreen, 2007). The lifetime risk of developing CRC is about 6% or one in 18. Over 95% of these CRC is adenocarcinoma (Kim et al, 2010). CRC is relatively uncommon in Indian sub continent. In India the incidence of colorectal cancer was found to be 4.2 and 3.2 per hundred thousand for male and female population respectively (Afroza et al, 2007).
The incidence of colorectal cancer in Bangladesh is not exactly known, it appears to be common and occur in younger age group with slight male preponderence. Average age at diagnosis is 10 years less than the developed countries. Rectal bleeding is the most common symptoms and majority of the carcinoma were in the rectum (Hossain, 2007). The peak incidence of colorectal carcinoma is in between the age of 60 and 69 years.Fewer than 20% occur before the age of 50 years. Males are affected slightly more than females (Turner, 2010). Colorectal carcinoma are rare before the age of 40 without genetic predisposition or without predisposing factors (Hamilton, 2000). Early detection of colonic cancers is a challenging task as because clinical symptoms develop slowly. Per rectal bleeding is common. Many patients experience change in bowel habit (Yawe et al, 2007). Screening tests like digital rectal examination, simple laboratoryinvestigations like estimation of CEA, estimation of haemoglobin, faecal occult blood test,and visualization of the gut mucosa by sigmoidoscopy and colonoscopy examination may be a help in the diagnosis (Aljebreen, 2007). Colorectal cancer is a multifactorial disease process. Etiology contributing from environmental factors including diatery factors, obesity, alcohol intake, smoking, life style and genetic and epigenetic abnormalities. The molecular events that leads to CRC is heterogenous and includes genetic and epigenetic abnormalities. Genetic events in colorectal cancer is genetic alteration of the APC gene, mutations in the KRAS and P53 gene and abnormalities in the DNA mismatched repair genes (Turner, 2010). Epigenetic changes, which is the heritable changes in gene function that are not due to changes in the DNA sequence is an important pathway in the mechanism of tumerogenesis in colorectal cancer. [...]
Table of Contents
1 INTRODUCTION
2 REVIEW OF LITERATURE
a Anatomical consideration
b Physiology
c Tumors of the colon and rectum
3 MATERIALS AND METHODS
4 OBSERVATIONS AND RESULTS
5 DISCUSSION
6 SUMMARY AND CONCLUSION
7 BIBLIOGRAPHY
8 APPENDICES
I Certificate from The Chicago University
II Clinical proforma
III Preparation of stains and chemicals
IV Tissue processing and staining procedures
V Protocol for DNA extraction
VI Protocol for DNA methylation
VII TNM staging system
VIII Master table
IX Illustrations
Research Objectives and Focus
The primary aim of this study is to examine the clinicopathologic patterns and epigenetic alterations, specifically DNA methylation, in colorectal carcinoma within a cohort of Bangladeshi patients, with the ultimate goal of identifying potential associations between molecular signatures and clinical outcomes.
- Evaluation of morphologic and histological characteristics of colorectal carcinoma cases.
- Analysis of clinical presentations and epidemiological data in the study population.
- Investigation of DNA methylation profiles in tumor tissue compared to adjacent normal tissue.
- Correlation of histopathological features, such as tumor grade and stage, with clinical variables.
- Identification of candidate genes showing significant methylation differences in colorectal cancer.
Auszug aus dem Buch
2.3.3.3 DNA methylation in cancer
Cancer results from the accumulation of mutation in the genes. In addition to genetic mutation, this epigenetic change has been included as an alternative mechanism to cancer development. Epigenetics refers to change in the pattern of gene expression by mechanisms other than alterations in the primary nucleotide sequence of a gene(Herman, 2003). DNA methylation is the enzymatic attachment of methyl group to the 5th carbon of the cytosine base (Samarakoon, 2010). Methylation usually occurs in the CpG islands, a cytosine guanosine rich region in the DNA. In humans, DNA methylation is carried out by a group of enzymes called DNA methyltransferases. The letter “p” here signifies that the C and G are connected by a phosphodiester bond. Methylation patterns in tumor cells are significantly different from those in normal cells (Herman, 2003).
Silencing or inactivation of tumour suppressor gene is seen in cancers mostly due to hypermethylation. Hypermethylation profiling over more than 15 tumor types (colon, stomach, pancreas, liver, kidney, lung, breast, ovary, endometrium, kidney, bladder, brain, and leukemia and lymphomas) has shown that all the metabolic pathways are affected by promoter hypermethylation-associated silencing. Hypomethylation leads to the inappropriate and increased levels of gene expression in tumors such as oncogene activation (Samarakoon, 2010).
Summary of Chapters
1 INTRODUCTION: Presents the global and regional epidemiology of colorectal cancer, emphasizing its rising incidence and the significance of epigenetic markers like DNA methylation.
2 REVIEW OF LITERATURE: Covers the anatomical, physiological, and pathological foundations of the colon, including tumor classification and current molecular understandings of colorectal carcinogenesis.
3 MATERIALS AND METHODS: Describes the study design, patient selection criteria, sample collection for histopathological and molecular analysis, and the laboratory techniques utilized.
4 OBSERVATIONS AND RESULTS: Provides a comprehensive data analysis regarding age, gender, clinical presentation, and specific DNA methylation findings in the studied patients.
5 DISCUSSION: Interprets the study results in the context of existing literature, discussing differences in age of onset and tumor characteristics in the Bangladeshi population.
6 SUMMARY AND CONCLUSION: Recapitulates the key findings of the study and offers concluding remarks on the role of DNA methylation in colorectal carcinoma pathogenesis.
Keywords
Colorectal cancer, DNA methylation, Epigenetics, Adenocarcinoma, Tumor grade, TNM staging, Hypermethylation, Hypomethylation, Bangladeshi population, Histopathology, CpG islands, Molecular pathogenesis, Oncology, Clinical presentation, Prognostic factors.
Frequently Asked Questions
What is the primary focus of this research?
This research focuses on investigating the clinicopathological features and DNA methylation patterns of colorectal carcinoma in a group of patients from Bangladesh.
What are the central themes discussed in this study?
The study revolves around colorectal cancer epidemiology, the molecular mechanism of DNA methylation in tumor development, histopathological tumor grading, and clinical staging.
What is the core research objective?
The objective is to determine the morphologic pattern, clinical presentation, and specific DNA methylation changes in colorectal carcinoma tissues compared to corresponding normal colonic tissues.
What scientific methods were employed?
The study utilized histopathological examination for tumor classification and grading, along with Infinium Assay technology to analyze genome-wide DNA methylation status in 24 paired tissue samples.
What topics are covered in the main body of the work?
The main body covers a comprehensive review of existing colorectal cancer literature, the methodological approach to data collection and molecular processing, detailed observational results of patient cases, and an analytical discussion comparing these findings to global trends.
Which keywords define this work?
The most defining keywords include colorectal cancer, DNA methylation, epigenetics, histopathology, and Bangladeshi patient population.
How do DNA methylation changes contribute to cancer development?
DNA methylation, specifically hypermethylation, can lead to the silencing or inactivation of tumor suppressor genes, while hypomethylation can lead to the inappropriate activation of oncogenes, both of which drive neoplastic transformation.
What did the study find regarding the age of onset in Bangladeshi patients?
The study observed that the average age at diagnosis in the studied Bangladeshi population is lower than that reported in many Western and other international studies.
What prognostic factors were analyzed in the colorectal cancer cases?
The study analyzed several prognostic factors including tumor stage, histological grading, lymphovascular invasion, circumferential margin involvement, and the presence of tumor-infiltrating lymphocytes.
What is the significance of the "Tumour differential score" mentioned in the results?
The tumor differential score helps quantify the significance of differences in methylation status between normal and tumor tissues, where positive values indicate hypermethylation and negative values indicate hypomethylation.
- Quote paper
- Dr. Abu Khalid Muhammad Maruf Raza (Author), 2010, Clinicopathologic pattern and DNA methylation status of colorectal carcinoma in a group of Bangladeshi patients, Munich, GRIN Verlag, https://www.grin.com/document/346420
