More than 100,000 cases of colon cancer occur in the United States each year. About 5 percent of these are linked to hereditary nonpolyposis colon cancer syndrome, or HNPCC, also called Lynch syndrome. The term "nonpolyposis" simply differentiates this syndrome from the polyposis syndromes, in which many---sometimes thousands---of polyps form in the colon, also called the large intestine.
Function of HNPCC Genes
Like all cancer syndromes, HNPCC increases a person's risk for a number of cancers and involves the inheritance of a changed gene that normally prevents cancer. HNPCC links with four genes involved in the mismatch repair pathway. This pathway normally identifies and corrects changes in genes to prevent cancer. If this pathway does not function, hundreds of errors in genes arise, along with failure to repair. This leads to the abnormal, unregulated cell growth that defines cancer.
Inheritance
HNPCC generally involves a gene mutation passed from one parent to child, with a normal working gene inherited from the other parent. Thus, the child inherits a risk of cancer, not cancer itself. When the normal working gene becomes nonworking, cancer begins. Parents with the HNPCC gene mutation have a 50 percent chance of passing the mutation with each child, regardless of their own cancer status.
Cancers in the HNPCC Syndrome
The MD Anderson Cancer Center reports that the main cancers seen with HNPCC include colon and endometrial cancers. Both men and women with HNPCC have up to an 80 percent lifetime risk for colon cancer, with diagnosis usually before age 50. Women further have increased lifetime risk---40 to 60 percent---for endometrial cancer, or cancer of the uterus. Other cancer risks with HNPCC include about a 30 percent lifetime risk for ovarian cancer and increased risks for cancers of the stomach, small intestine, liver and kidney.
Defining HNPCC
Different criteria determine the presence of HNPCC. According to the American Society of Clinical Oncology, the classic criteria are as follows: three or more relatives with an HNPCC-related cancer, as named above, with one relative a first-degree relative of the other two; at least two generations with cancer; and one or more cases of cancer diagnosed before age 50. Patients meeting these criteria proceed to genetic testing to confirm HNPCC.
Risk Reduction
Surgical procedures can reduce HNPCC cancer risks. Those who develop colon cancer generally proceed to full colectomy, or removal of the entire colon. Prophylactic removal of the colon, or surgical removal of the colon before cancer occurs, generally does not occur in favor of surveillance options. Other surgical options include prophylactic removal of the uterus and ovaries. Alternative to surgery, surveillance to find cancer early includes colonoscopy every one to two years beginning by age 25 or 10 years before the earliest age of cancer diagnosis in the family. Surveillance for cancers of the uterus, ovary, stomach, small intestine and other cancers associated with HNPCC exists, but its effectiveness has not been proven.
