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 the 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.
A small percentage of cases of colon cancer are due to inherited factors. The two most common colorectal cancer syndromes associated with genetic mutations are familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer (HNPCC). Genetic tests can help screen for mutations associated with these syndromes.
Familial Adenomatous Polyposis (FAP). Familial adenomatous polyposis is caused by mutations in a tumor suppressor gene called APC. When the adenomatous polyposis coli (APC) gene is normal, it helps suppress tumor growth. In its defective form, it accelerates cell growth leading to polyps. The APC mutation can be inherited from either parent. People with FAP develop hundreds to thousands of polyps to in the colon. FAP causes less than 1% of all cases of colorectal cancer. If FAP is left untreated, however, virtually everyone who inherits this condition develops cancer by age 45. Polyps usually first appear when people with FAP are in their mid-teens. FAP also increases the risks for other types of cancers including stomach, thyroid, pancreatic, liver, and small intestine cancers.
Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, accounts for 3 - 5% of all colorectal cancers. About 50 - 80% of people who inherit the abnormal gene develop colon cancer by age 45. HNPCC is caused by mutations in MLH1, MSH2, MSH6, and PMS2 genes. People with HNPCC are prone to other cancers, including uterine and ovarian cancers, as well as cancers of the small intestine, liver, urinary tract, and central nervous system.
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