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Concept
Hereditary nonpolyposis colorectal cancer
Summary
Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited genetic mutations that impair DNA mismatch repair. It is a type of cancer syndrome. Because patients with Lynch syndrome can have polyps, the term HNPCC has fallen out of favor.
Lifetime risk and mean age at diagnosis for Lynch syndrome associated cancers
In addition to the types of cancer found in the chart above, it is understood that Lynch syndrome also contributes to an increased risk of small bowel cancer, pancreatic cancer, ureter/renal pelvis cancer, biliary tract cancer, brain cancer, and sebaceous neoplasms. Increased risk of prostate cancer and breast cancer has also been associated with Lynch syndrome, although this relationship is not entirely understood.
Two-thirds of colon cancers occur in the proximal colon and common signs and symptoms include blood in the stool, diarrhea or constipation, and unintended weight loss. The mean age of colorectal cancer diagnosis is 44 for members of families that meet the Amsterdam criteria. The average age of diagnosis of endometrial cancer is about 46 years. Among women with HNPCC who have both colon and endometrial cancer, about half present first with endometrial cancer, making endometrial cancer the most common sentinel cancer in Lynch syndrome. The most common symptom of endometrial cancer is abnormal vaginal bleeding. In HNPCC, the mean age of diagnosis of gastric cancer is 56 years of age with intestinal-type adenocarcinoma being the most commonly reported pathology. HNPCC-associated ovarian cancers have an average age of diagnosis of 42.5 years-old; approximately 30% are diagnosed before age 40.
Significant variation in the rate of cancer has been found depending on the mutation involved.
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