Colon Cancer

Carcinogenesis is the process by which cancer is produced. Carcinogenesis is caused by genetic damage to cells. It is not an infectious process. (Note: certain infectious diseases that are transmissible from person to person may create conditions that permit cancer to develop, but the cancer cells themselves are not infectious.)

Genetic material is contained in the cell nucleus. It consists of deoxyribonucleic acid, or DNA. DNA is involved in the reproduction of the cell and how it functions (that is, what type of organ it will be part of and what it will do in that organ) and determines most of the attributes of the living organism. The cell is bounded by a membrane, which serves as a site of receptors for hormones and proteins from other cells that may send signals to the cell. The membrane, by virtue of the physical barrier that it creates and the receptor molecules that are located on it, also serves as a gatekeeper that keeps out or permits molecules to enter the cell cytoplasm.

All cancers begin with cells that have accumulated genetic changes, or mutations, which cause the cells to lose normal control of reproduction and differentiation (maturation to their specific individual form and function). These abnormal cells produce progeny that have the same mutations. The majority of colon cancers are the result of either inherited genetic abnormalities that predispose a person to cancer or the accumulation of cancer-producing mutations under the steady influence of environmental stresses. We will be discussing these pathways to cancer in further detail below.

Cancer is a disease of uncontrolled cell reproduction and loss of differentiation. Current theory holds that carcinogenesis is due to cells losing through a series of mutations the ability to regulate cell death. These immortal cells have lost the ability to undergo the genetically programmed process known as apoptosis, which permits a cell to complete its natural life cycle. Cancerous cells may therefore both proliferate and accumulate. Cells that are relatively old are prone to accumulate further genetic damage from exposure to genotoxins such as drugs and radiation. Cells may therefore be susceptible to further instability and malignancy. The immortal cells of cancer, much like vampires, eventually kill the organism that feeds them.Carcinogenesis is a slow process. Cancer does not develop in a matter of hours or days or even weeks. Multiple phases are involved in carcinogenesis that may take years or even decades to evolve. The steps in colon carcinogenesis beginning with a normal cell and ending with a clinically apparent cancer may be summarized as follows:

1. Initiation. In this phase a normal cell is “initiated” into the path towards malignancy by a mutation.
2. Clonal expansion. The cells do not yet appear neoplastic (cancerous), but have accumulated as clones which make them ready to take the next step toward cancer. In colon carcinogenesis, this may appear as aberrant crypt foci in the mucosal epithelium.
3. Benign tumor formation. Further genetic changes have turned a preneoplastic clone into a benign neoplasm (tumor). In colon cancer, this is the polyp phase (also known as adenoma or adenomatous polyp).
4. Malignant tumor. Further mutations in the cells of an adenomatous polyp have converted it to a malignant tumor.
5. Clinical cancer. The malignant tumor has now acquired the properties of what is clinically referred to as cancer: the tendencies to invade and to metastasize (spread).

Research suggests that the average time of progression from initiated cell to adenomatous polyp is five years. The same amount of time is probably required for an adenomatous polyp to become invasive cancer. The long amount of time between adenoma and cancer provides the rationale for colon cancer screening. If polyps are detected early, the progression to cancer can be stopped.
Certain individuals are genetically predisposed to develop colon cancer. Such individuals have a colon composed entirely of cells which already are “initiated.” Sporadic colon cancer, on the other hand, requires the cumulative acquisition of mutations in colonic mucosal cells that result in cancer formation. The accumulation of these mutations requires the influence of environmental (mostly dietary) factors. The risk of occurrence of such an accumulation of mutations in the general American public is estimated to be about 5 percent.

When someone speaks of colon cancer, it is understood that the specific category of cancer being referred to is an adenocarcinoma. This type of cancer arises from the mucosa of the large bowel. While benign and malignant tumors can arise from other cell types such as muscle (known as leiomyomas and leiomyosarcomas) and lymphocytes (lymphomas), these are quite rare. Adenocarcinoma refers to the glandular nature of the cells and tissue from which it derives. (Adenos is the Greek word for gland; carcinoma refers to an epithelial malignancy.)