Methyl-altered DNA and Colon Cancer
(This is a science-fiction article)
Jim had been diagnosed with ulcerative colitis when he was 29. His doctor, Dr. Leonard McCoy, told him
that it was not common to get colitis at such an age and that he should be aware that the chronic inflammation that is one of the symptoms of ulcerative colitis put him at higher risk of developing colon cancer. As Jim aged, he had periodic flare ups that would be treated with courses of prednisone, a powerful steroid, that would reduce the inflammation and pain.
When Jim was 42, Dr. McCoy told him that there was a new test** that could predict his risk of colon cancer. Since Jim had now had colitis for 13 years, he was past the recommend time to have his colon removed to cure his colitis and to prevent colon cancer. The first clinical sign of ulcerative colitis-related colon cancer is dysplasia, an abnormal condition of the mucous membrane in the colon, and Jim was still clear of this condition, but Dr. McCoy was concerned because Jim had had ulcerative colitis for so long and that he was over forty years old, putting him at higher risk for having the colectomy and the pelvic pouch that would be constructed to replace it. Also, he had gained a lot of weight as a side effect of taking prednisone so frequently.
This new test was designed to detect the hypermethylation of several different genes that were involved 
in the development of colon cancer and that were associated with long-term ulcerative colitis. Dr. McCoy recommended that Jim have this test that consisted of taking several biopsies of the colonic mucosal membrane and of polyps that had developed due to the chronic inflammation. Since having the colonoscopy that would be necessary to take the biopsies was rather painful, Jim was somewhat reluctant to have the test and asked the Dr. McCoy explain what hypermethylation was and if there was any alternative.
Dr. McCoy first explained that this was the only test that had been developed that could predict the risk
of colon cancer before dysplasia could be detected; and that once dysplasia was present and could be seen, it might be too late and cancer may already be present as well. Depending on how long the cancer had been present, it could have already metastasized and spread to other places in his body, making the failure of treatment and death more likely.
“Methylation,” he said, “is a process that can happen for a number of reasons. The inflammation associated with ulcerative colitis being one of them. What happens is that a methyl group attaches to a site in the genomic DNA in a cell, actually altering the DNA. When this happens it affects the expression of the particular gene, either causing to create or not create a protein it normally would or wouldn’t. Once methylation occurs in a cell, when that cell divides, the methylated site is passed on to the new cell. If the rate of production of cells with this methylated gene exceeds the death rate of these cells, increasing the percentage of cells that have the methylated DNA and the risk of cancer. The test can 
detect the methylation sites and the degree to which the tissue has become methylated, a small amount is normal so what we would be looking for is a significantly higher level of methylation. It really is no worse than a normal colonoscopy. Actually, I take biopsies routinely anyway, ever since you began developing polyps. If the test comes back positive, it becomes all that more important for you to have your colon removed. You aren’t getting any younger you know.”
“Okay, I guess I’ll have the test. Ugh, how I hate colonoscopies,“ Jim complained in a subdued tone.
** Please note: This is a fictional story. Although the content is factual, the characters from Star Trek and their conversation are fictional. Also, the test is not available for patients. It has been used for research only.
Read More: CpG Methylation in Ulcerative Colitis
Hypermethylation in Long-standing Ulcerative Colitis
(This is a science-fiction article)
April 16th, 2010 at 9:52 am
You give hope to all those who suffer with this. Thanks for a great post and a great site.