Alternative Names
Cancer Family Syndrome; COCA 1; Familial nonpolyposis colon cancer; Hereditary nonpolyposis colorectal cancer; Hereditary Nonpolyposis Colorectal Neoplasms; HNPCC; Lynch Syndrome I; Lynch Syndrome II
Symptoms & Characteristics
Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is a type of hereditary cancer of the digestive tract, particularly the colon (large intestine) and rectum. People with Lynch syndrome have an increased risk to develop cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, and prostate. Women with this disorder also have a high risk of cancer of the endometrium (lining of the uterus) and ovaries. Even though the disorder was originally described as not involving noncancerous (benign) growths (polyps) in the colon, people with Lynch syndrome may occasionally have colon polyps. In individuals with this disorder, colon polyps occur at an earlier age than in the general population. Although the polyps do not occur in greater numbers than in the general population, they are more likely to become cancerous.
Treatment
Early diagnosis and routine surveillance may help to detect early stage colorectal cancer, when treatment is more likely to be effective.
How Common Is It?
In the United States, about 160,000 new cases of colorectal cancer are diagnosed each year. Approximately 2% to 7% of these cancers are caused by Lynch syndrome.
Genetics & Inheritance
Variations in the MLH1, MSH2, MSH6, and PMS2 genes increase the risk of developing Lynch syndrome. All of these genes are involved in the repair of mistakes made when DNA is copied (DNA replication) in preparation for cell division. Mutations in any of these genes prevent the proper repair of DNA replication mistakes. As the abnormal cells continue to divide, the accumulated mistakes can lead to uncontrolled cell growth and possibly cancer. Although mutations in these genes predispose individuals to cancer, not all people who carry these mutations develop cancerous tumors.
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MLH1 and MSH2 mutations account for approximately 90% of families with Lynch syndrome.
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MSH6 mutations account for approximately 7% to 10% of families with Lynch syndrome.
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PMS2 mutations account for fewer than 5% of families with Lynch syndrome.
Mutations in the TFGBR2, MLH3, and PMS1 genes have also been reported in some families with Lynch syndrome. However, the clinical significance of these genes in Lynch syndrome has not yet been firmly established, and clinical genetic testing is not available.
Lynch syndrome cancer risk is inherited in an autosomal dominant pattern, which means one inherited copy of the altered gene in each cell is sufficient to increase cancer risk. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer.
Genetic Testing
Cancer predisposition testing for Lynch syndrome may be available through an in person genetic consultation for people who are considered at risk.
There is considerable debate and concern regarding testing of at-risk individuals younger than age 18 years old for adult-onset conditions (including Lynch syndrome). Such testing is typically unavailable. The American Society of Human Genetics in conjunction with the American College of Medical Genetics as well as the National Society of Genetic Counselors have issued statements regarding this type of testing:
The decision to have genetic testing is personal and should always be discussed with trained medical professional. Use our find a genetic professional directory to locate a trained genetic professional in your area.
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