Approximately 147,000 new cases of colorectal cancer (CRC) are diagnosed each year in the United States, affecting over 5% of the US population. However, colorectal cancer is one of the most potentially preventable cancers. Screening is critical for prevention and should be a part of routine care for adults over the age of 50 who are at average risk. High-risk individuals, those with previous colon cancer, family history of colon cancer or history of colorectal polyps require heightened surveillance and management. Colorectal cancer occurs when the cells that line the colon or the rectum become abnormal and grow out of control. This cell growth usually leads to the formation of polyps. Polyps are usually benign growths that protrude from a mucous membrane that can form in the colon and rectum. Polyps that are adenomatous may eventually progress into cancer if left untreated.

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is the most common of the hereditary colorectal cancer syndromes. Clinical features of HNPCC include a tendency to develop colorectal cancer at an early age and, many times, the cancer occurs on the right side of the colon. It is important to note that CRC associated with mutations in MLH1 and MSH2 is often diagnosed before age 50 (mean age of onset is 41-44 years), whereas CRC in patients with MSH6 mutations may occur a bit later (mean age of onset is 55-57 years).

Individuals with HNPCC will have adenomatous polyps but not in large numbers. These adenomas show a rapid progression to colorectal cancer when compared to sporadic colon cancer. Tumors are of high grade but several studies have found an improved prognosis compared to sporadic colorectal cancers. Synchronous and metachronous CRC is far more common in HNPCC than in sporadic CRC. The tumors characteristically occur in the right, proximal end of the colon, are more poorly differentiated and usually demonstrate microsatellite instability (MSI).

In addition to colorectal cancer, HNPCC is also associated with an increased risk of endometrial cancer in women. Endometrial cancer is the fourth most common cancer in women; about 40,000 women are diagnosed with endometrial cancer each year. Endometrial cancer associated with mutations in MLH1 and MSH2 often occurs prior to age 50 (mean age of onset is 48-49 years). As with CRC, endometrial cancers in MSH6 mutation carriers may occur a bit later (mean age of onset is 54-55 years). This is in contrast to sporadic endometrial cancer, which usually occurs after age 60.

The risk for other cancers in HNPCC is greatly increased. In addition to CRC and endometrial cancer, there is an increased risk for cancers of the ovary, stomach, ureter/renal pelvis, biliary tract, small bowel, pancreas, brain, and sebaceous adenomas.

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