Question 1 -10 marks (300 words)
Describe the pathogenesis of Brian’s colorectal cancer from the initial cellular mutation to the diagnosis of stage IIA colorectal cancer (Learning outcome 5).
Cells have a control centre called a nucleus. Inside the nucleus are chromosomes made up of long strings of DNA. DNA contains thousands of gene, which are coded messages that tell the cell how to behave. It starts with epigenetic alterations, it alter the physical structure of DNA (DNA methylation). This event can cause for activation of proto-oncogenes, chromosomal instability and inactivation of tumour-suppressor genes. It also inactivates the APC gene, which allows unchecked cellular replication at the crypt surface. Increased cell division leads to activation of the K-ras oncogenes in the early stages and p53 mutations in later stages. Cumulative losses in tumour suppressor gene function prevent apoptosis and prolong the cell’s lifespan indefinitely.
Most of colorectal carcinomas evolve from adenomatous polyps. The formation of a neoplastic process requires cumulative genetic alterations. There are three mutation involved. First mutations in proto-oncogenes that induce their transformation into active oncogenes. Second mutations or deletions that reduce the activity of tumour suppressor genes. Third mutations that cause damage involved in DNA repair. These three mechanism contribute to uncontrolled cell proliferation, autonomous growth and, therefore, tumor formation. It is assumed that the neoplastic process starts along with the intracellular expression of the first genetic mutations and, as the genetic damage continues to accumulate, the neoplastic process becomes more advanced. David’s tumour is classified using tumour/node/metastases (TNM) classification. He was diagnosed as Stage 2a, which means cancer growth into the outer covering of the bowel wall T3: invades subserosa or non-peritonealised pericolic tissues. N0: no regional nodes involved. M0: no distant metastasis.
Question 2 -10 marks (300 words)
Describe two modifiable and three non-modifiable risk factors for colorectal cancer and explain how these risk factors may have contributed to the development of Brian’s colorectal cancer. Modifiable factors:
a. Diet: high consumption of grilled and charred red meat. When the proteins are heated to the point that the flesh starts to brown and blacken, you have the presence of heterocyclic amines (HCA), some of which are known carcinogens. These chemicals directly damage DNA, our genetic material, and initiate mutations that can lead to the development of cancer.
b. Alcohol consumption impairs the body’s ability to break down and absorb a variety of nutrients that may be associated with cancer risk, including vitamin A; nutrients in the vitamin B complex, such as folate; vitamin C; vitamin D; vitamin E making the tissue susceptible to carcinogenesis.
a. Age – as people age, aged immune system is not as efficient in recognizing and eliminating new invaders or in preventing their spread - as we age, we accumulate a lot of DNA mutations that give us a higher risk to cancer b. Familial history/Genes – Familial adenomatous polyposis is an inherited condition of colonic polyps that leads to early colorectal carcinoma. c. Past history of IBD - inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a condition in which the colon is inflamed over a long period of time. People who have had IBD for many years often develop dysplasia. Dysplasia is a term used to describe cells in the lining of the colon or rectum that look abnormal (but not like true cancer cells) when seen with a microscope. These cells can change into cancer over time.
Question 3 -5 marks (150 words)
a.) Describe the action and mechanism of action of metronidazole (Flagyl) in relation to its administration to Brian.
It inhibits nucleic acid