A 65-year-old woman comes to the office after finding blood in her stool. She is physically active and exercises regularly. She does not use tobacco or alcohol. She has no history of peptic ulcer disease. Her physical examination is unremarkable. Colonoscopy reveals several large adenomatous polyps with severe dysplasia in the sigmoid colon. She undergoes resection of the sigmoid colon, and her carcinoembryonic antigen level is normal. The patient is interested in decreasing her chances of developing new polyps and colon cancer. The physician discusses exercise, healthy weight, and dietary factors associated with reduction of colon cancer risk, including increased fiber intake and reduced consumption of refined sugars and fat. Which of the following enzymes could be inhibited with medication to further reduce this patient's risk of developing recurrent adenoma?

Question

A 65-year-old woman comes to the office after finding blood in her stool.  She is physically active and exercises regularly.  She does not use tobacco or alcohol.  She has no history of peptic ulcer disease.  Her physical examination is unremarkable.  Colonoscopy reveals several large adenomatous polyps with severe dysplasia in the sigmoid colon.  She undergoes resection of the sigmoid colon, and her carcinoembryonic antigen level is normal.  The patient is interested in decreasing her chances of developing new polyps and colon cancer.  The physician discusses exercise, healthy weight, and dietary factors associated with reduction of colon cancer risk, including increased fiber intake and reduced consumption of refined sugars and fat.  Which of the following enzymes could be inhibited with medication to further reduce this patient's risk of developing recurrent adenoma?

Quizplus · Accepted Answer

11ec160b_393b_bc56_9249_97077744b800_MD0001_00 Adenomatous polyps contain dysplastic mucosa and are premalignant. They tend to develop in patients age >50 as a result of mutations in the APC tumor suppressor gene, which regulates cell growth and adhesion. Progression to adenocarcinoma proceeds as other mutations occur in genes such as KRAS and TP53. This accumulation of gene mutations is called the "adenoma-to-carcinoma sequence." Increased activity of the enzyme cyclooxygenase-2 (COX-2) has been found in many forms of colon adenocarcinoma and in inherited polyposes syndromes. This may be due to the need for COX-induced prostaglandin production, which leads to epithelial proliferation. Regular aspirin (a COX inhibitor) intake has been associated with lower rates of colonic adenoma and adenocarcinoma, although this must be balanced against bleeding risk. (Choice A) Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II, which plays an important role in hypertension and congestive heart failure. ACE inhibitors are widely used to treat these conditions. (Choice B) Caspases are cysteine proteases that are an essential component in cellular apoptosis. Inhibition of caspase activity would lead to cells that are resistant to apoptosis; this is one of the mechanisms involved in the progression of the adenoma-to-carcinoma sequence. (Choices D and E) Glutamate dehydrogenase (produces ammonia for use in the urea cycle) and phenylalanine hydroxylase (converts phenylalanine to tyrosine) have not been implicated in the development of adenomatous polyps. (Choice F) Xanthine oxidase is an enzyme that participates in uric acid synthesis. Allopurinol is a xanthine oxidase inhibitor used to lower serum levels of uric acid in gout and tumor lysis syndrome. Educational objective: Adenomatous polyps contain dysplastic mucosa and are premalignant. Regular screening with timely excision of polyps is effective for prevention of colon adenocarcinoma. Studies have linked increased activity of cyclooxygenase-2 to some forms of colon adenocarcinoma and suggest that regular aspirin use decreases adenomatous polyp formation. __________ References: Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma (http://www.ncbi.nlm.nih.gov/pubmed/18230181) Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. (http://www.ncbi.nlm.nih.gov/pubmed/17522398) Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials (http://www.ncbi.nlm.nih.gov/pubmed/19211452) Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer (http://www.ncbi.nlm.nih.gov/pubmed/24074752)

A 65-Year-Old Woman Comes to the Office After Finding Blood