Colon Cancer NOT for Dummies.


Colon Cancer NOT for Dummies.

Before you read any further, be warned.  What you are about to read is in-depth, scientific, specific and detailed information about cancer.  If you prefer your reading to be “less technical” stop now.  For those of you who want the “nitty gritty” read on.

Differentiating sclerotic colon cancer from inherited colon cancer.

For every 100 people who develop colon cancer in this country, approximately 75 are termed sclerotic colon cancer.  This means there appears to be no genetic predisposition – no history of cancer in the immediate family.  These patients are thought to have a sporadic mutation. Initially, the loss of the APC suppressor gene (it regulates the cell division cycle by keeping cells from growing and dividing too fast or in an uncontrolled way which ultimately can allow cancer cells to form) allows the formation of a polyp. This may be the only change followed by K-ras gene activation leading to the polyp becoming an adenoma, the first step before cancer development. This is followed by loss of the DCC gene and P. 53 mutation leading to development of cancer. About 13-17 percent of sporadic cancers involving a different mechanism of what is termed microsatellite instability or MSI which is associated with a mutation leading to abnormality in the MMR system. The MMR or mismatch repair system is the product of an enzyme complex located within the cell nucleus in every cell of our body but constantly repairs mutations in the cellular genome. Every time DNA is in the process of being copied either for cellular replication (development of a new cell or for production of a protein such as the proteins necessary for regulating in preventing tumor development), there is a possibility for mismatch.  As the code is being copied, there is a natural air arranged with the wrong base pare placed into the DNA sequence. As the proteins are being produced or asked, the cellular template is being copied.  These mismatch repair gene proteins are reading both the original blueprint as well as the new chain of DNA being produced.  The new RNA will become part of the DNA when an air is encountered between the parent template and the daughter.  New production of the MMR system is able to excise the abnormal area. Undetected errors result in mutations that in time can lead to cancer development.  Therefore it is failure of the mismatch repair system that leads to a condition called microsatellite instability leading to the chain of events of 5-7 mutations necessary to turn normal tissue into colon cancer, involving subsequently all of the issues mentioned above.

This microsatellite instability gene, while present in only about 13-17 percent of sporadic colon cancers, is present in all cases of the largest group of inherited colon cancers, which are associated with a condition called Lynch syndrome or NPH CC.  This stands for non-polyposis hereditary colon cancer. Lynch syndrome is also associated with malignancies of the endometrium as well as nervous system gastric and pancreatic biliary tumors

There is another hereditary group of colon cancers accounting for only about 1 percent of colon cancers nationally termed FAP or familial adenomatous polyposis.  Individuals affected will have more than 100 polyps, sometimes several thousand.  These polyps will tend to result in colon cancer at a much younger age.  Even in the early 20s it is recommended with this diagnosis to undergo removal of the entire colon to avoid colon cancer risk. This type of colon cancer is associated with a defect in the APC gene which is the tumor suppressor gene and is also associated with other tumors outside of the GI tract including the desmoid tumors and bone cysts particularly in facial area one variation of which is called Gardner syndrome.

The most important thing to note from all of this is that colon cancer is derived from completely normal tissue because of mutations occurring in individual cells that may lead to activation of tumor activating factors or suppression of tumor suppressing factors by means of genetic mutations. A single individual cell becomes clonal, meaning it begins to copy itself without regulation to its growth pattern for the usual biologic clock associated with that tissue type.  It basically grows wildfire out-of-control and the most important thing to remember about this is there is a very finite point where this process -- even begun -- can still be halted by removal of the entire mass of abnormal clonal cells, even when it is still a polyp which is optimal.  There is however, a single finite time when the polyp becomes cancer and still often there is time but, there is a single finite moment in time at which a single cell breaks free from the intestinal lining, either into the lymph nodes that were spreading distantly through the blood stream or the lymphatic channels into other organs. It is at this very moment the survivability drops precariously. I am often amazed when upon telling the patient they have colon cancer they will sometime say this is not a good time for me to deal with this what I were to wait 3 or 4 months. Knowing what I know about colon cancer I would be reluctant to let a week ago by from the time of diagnosis to surgery.

I cannot overemphasize the importance of early screening early detection early removal in the process of prevention of this almost entirely preventable and otherwise ghastly disease. Therefore in the spirit of colon cancer awareness of screening month please schedule your colonoscopy if you've met screening criteria.