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Colon and rectal cancers

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of colorectal cancer.

Alternative Names

Colorectal cancer

Causes

In most cases of colon or rectal cancers the cause or causes are unknown. Defects in genes that normally protect against cancer play the major role in causing polyp cells to continuously spread and become cancerous. Some of these cases are caused by inherited genetic defects, and such patients usually have family histories of colorectal cancer. Most of genetic mutations involved in colon cancers, however, appear to arise spontaneously (no strong family history) rather than being inherited. In such cases, environmental or other factors trigger genetic changes in the intestine that lead to cancer.

Inherited Genetic Factors

About 6% of cases of colon cancer are due to inherited facts.

APC Gene and Familial Adenomatous Polyposis (FAP). When the adenomatous polyposis coli (APC) gene is normal, it helps suppress tumor growth. In its defective form, it permits high levels of the protein beta-catenin to accumulate, which accelerates cell growth leading to polyps. Various genetic mutations that affect the APC gene directly or indirectly have been identified:

• Familial adenomatous polyposis (FAP) is a rare and serious disorder in which the patient inherits an APC mutation from either parent. It occurs in about 1 in 8,000 people. During early adulthood, hundreds to thousands of polyps grow in the colon. FAP causes less than 1% of all cases of colorectal cancer, but if untreated, virtually everyone who inherits this condition develops cancer before the age of 40. Many of the deaths attributed to FAP can be prevented with early and aggressive surgical treatment.
• Non-inherited mutations of the APC gene have been detected in nearly all patients with spontaneous colon cancers.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, accounts for at least half of colorectal cancers that run in families. (However, only 3% or less of all colorectal cancers are due to this problem). About 50 - 80% of people who inherit the abnormal gene will develop colon cancer. HNPCC tends to develop in the right side of the colon, often in young individuals. (Left-sided cancers can still occur as well.)

People who inherit HNPCC and other defects are prone to other cancers, including uterine and ovarian cancers, as well as cancers of the small intestine and kidney system (very rare). HNPCC is highly associated with genes containing an abnormality called MSI (microsatellite instability), which is a sign of defective DNA repair. Testing tumors for MSI in people with newly diagnosed colon cancer who also have a family history of the disease may prove to be an effective method for identifying patients with HNPCC. Tests are being developed that can detect the actual HNPCC genetic abnormality (mutation) that was inherited from a father or mother. The two most commonly affected genes are MSH-2 and MLH-1.

Biochemical Factors Involved in Colon and Rectal Cancers

Cyclooxygenases and Prostaglandins. Cyclooxygenase 1 and 2 (COX-1 and COX-2) are enzymes involved in the production of prostaglandins, substances produced by the body that cause inflammation, widen and narrow blood vessels, control muscle contractions, and inhibit hormones that regulate fat metabolism. COX-2, but not COX-1, appears to play a role in the development and spread of colorectal tumors. COX-2 increases the levels of prostaglandin E2 (PGE2), which, in turn, stimulates factors that inhibit apoptosis, the natural process whereby all cells, including cancerous ones, self-destruct. It also activates interleukin-6 (IL-6), a factor in the immune system that is associated with cancer cell invasion.

C-Reactive Protein (CRP). CRP is another indicator of inflammation. In a 2004 study published in the Journal of the American Medical Association , elevated CRP levels predicted the development of colon -- but not rectal -- cancer.

Bile Acid Salts. Deoxycholic acid, which is found in the fat-digesting bile salts released by the gallbladder, appears to have carcinogenic properties. Its effects are now believed to play a role in some cases of colon cancer. Levels of the acid can rise as a result of high-fat diets or certain diseases.

Growth Factors. Chronically higher circulating levels of growth factors, including insulin-like growth factor (IGF), have been associated with colorectal cancer.

Inflammatory Bowel Disease

Inflammatory bowel diseases (IBDs) include Crohn's disease and ulcerative colitis. These chronic disorders cause persistent injuries in the intestinal tract that can, in some cases, produce cancerous changes.

• Review Date: 3/6/2007
• Reviewed By: A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (9/1/2006).

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