What is hereditary non-polyposis colorectal cancer?
Hereditary non-polyposis colorectal cancer (HNPCC) is also known as Lynch syndrome. HNPCC may be a possible diagnosis when there are multiple cases of colorectal cancer on the same side of the family. Other types of cancer seen in families with HNPCC are endometrial (uterine), stomach, ovarian, small bowel (intestinal), urinary tract, liver, and bile duct cancers. People who have HNPCC have a significantly increased risk of developing colorectal cancer and an increased risk of developing the other cancers mentioned. Cancer is more likely to be diagnosed at a young age. The average age for colorectal cancer to be diagnosed in someone with HNPCC is 45, as compared with the average age of 72 for a new diagnosis of colorectal cancer in the general population. In HNPCC, the colorectal cancer is somewhat more likely to develop on the right side of the colon. There is also an increased risk of a person with HNPCC to develop multiple cancers during his or her lifetime.
The classic diagnostic criteria for HNPCC are called the Amsterdam Criteria. Over time, the Amsterdam Criteria have been modified to include the variety of cancers that are seen in HNPCC families. The Modified Amsterdam Criteria, also known as the Amsterdam II Criteria, are listed below:
- Three or more relatives with an HNPCC-related cancer;* one relative must be a first-degree relative (parent, brother, sister, or child) of the other two
- At least two generations with cancer (such as a parent and child)
- One or more cases of cancer diagnosed younger than age 50
- Familial adenomatous polyposis (FAP) is ruled out as the cause
*(colorectal cancer, endometrial cancer, small bowel, ureter, or renal pelvis cancer; some people would also consider including ovarian cancer)
The definition of HNPCC is still evolving. A family may still have HNPCC even if the Amsterdam Criteria does not fully match the family history. Therefore, meeting with a health professional who specializes in genetics, such as a genetic counselor or medical geneticist, is recommended for people who have a family history that suggests HNPCC. Learn more about what to expect when meeting with a genetic counselor.
There are two variant forms of HNPCC called Muir-Torre syndrome and Turcot syndrome.
What causes HNPCC?
HNPCC is a genetic condition. This means that the cancer risk can be passed from generation to generation in a family. Several genes have been identified that are linked to HNPCC. They include MLH1, MSH2, MSH6, and PMS2. A mutation (alteration) in any of these genes gives a person an increased lifetime risk of developing colorectal cancer and other related cancers. Women also have an increased risk of developing endometrial and ovarian cancers. Most mutations that cause HNPCC are found in the MLH1 or MSH2 genes. Not all families that appear to have HNPCC will have mutations in MLH1, MSH2, MSH6, or PMS2. Research is ongoing to identify other genes associated with HNPCC. Some people will develop changes in these genes that are not inherited, but are related to the aging process and other causes that are not well understood. If a tumor is found to have alterations in these genes, the person’s blood will also be tested for that abnormal gene. If the blood and tumor both have the changed gene, the condition is inherited rather than acquired, and family members can be tested.
How is HNPCC inherited?
Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. HNPCC follows an autosomal dominant inheritance pattern, in which a mutation needs to happen in only one copy of the gene for the person to have an increased risk of getting that disease. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.
How common is HNPCC?
Most colorectal cancer is sporadic (occurs by chance with no known cause). Approximately 3% to 5% of all cases of colorectal cancer are thought to be due to HNPCC.
How is HNPCC diagnosed?
HNPCC is likely if a family history meets the Modified Amsterdam Criteria listed above. HNPCC can be confirmed through a blood test. The test can determine if someone has a mutation in one of the genes associated with HNPCC. Currently testing is available for the MLH1, MSH2, and MSH6 genes. The PMS2 gene is tested for in some clinical trials as well as cancer centers that specialize in HNPCC. However, not all families with HNPCC will have a mutation in one of these four genes.
For patients who have a family history that suggests HNPCC, screening tests can be performed on tumor (cancer) tissue to help determine if HNPCC is likely. The two screening tests suggested are microsatellite instability testing (MSI) and immunohistochemistry testing (IHC). The results of these tests can indicate whether more specific genetic testing should be considered.
Since most colorectal cancer is sporadic, genetic testing is only recommended for people who have a family history that suggests HNPCC. Testing for mutations in the HNPCC genes may not be beneficial for the average person.
What are the estimated cancer risks associated with HNPCC?
General cancer risks for people with HNPCC
|
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80% |
|
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11% to 19% |
- Hepatobiliary tract (liver/bile duct)
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2% to 7% |
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4% to 5% |
|
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1% to 4% |
- Brain or central nervous system
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1% to 3% |
Cancer risks for women with HNPCC
What are the screening options for HNPCC?
It is important to discuss with your doctor the following screening options, as each individual is different:
General screening guidelines
- Colonoscopy every one to two years, beginning between the ages of 20 to 25 (or five years younger than the earliest age at diagnosis in the family, whichever is sooner)
- Periodic upper endoscopy screening for stomach or intestinal cancer (especially if a family member has had one of these cancers)
- Yearly urinalysis to screen for urinary tract cancer
Screening for women
- Yearly pelvic examination, Pap test, transvaginal ultrasound (a test where an small ultrasound probe is inserted for a pelvic examination in order to obtain better imaging of the uterus), endometrial biopsy (an examination on a sample of tissue from the inner lining of the uterus done as a part of a pelvic examination), and CA-125 blood test (a test to detect a protein found to be elevated in the blood of some women with ovarian cancer), beginning between the ages of 25 to 30
Screening options may change over time as new technologies are developed and more is learned about HNPCC. It is important to talk with your doctor about appropriate screening tests.
Learn more about what to expect with common tests and procedures.
Questions to ask the doctor
If you are concerned about your risk of colorectal cancer or other types of cancer, talk with your doctor. Consider asking the following questions of your doctor:
- What is my risk of developing colorectal cancer or other types of cancer?
- What can I do to reduce my risk of cancer?
- What are my options for cancer screening?
If you are concerned about your family history and think your family may have HNPCC, consider asking the following questions:
- Does my family history increase my risk of colorectal cancer or other types of cancer?
- Have MSI or IHC tests been done on my tumor tissue?
- Should I meet with a genetic counselor?
- Should I consider genetic testing?
Additional resources
Guide to Colorectal Cancer
The Genetics of Colorectal Cancer
Guide to Uterine Cancer
Guide to Stomach Cancer
Guide to Ovarian Cancer
The Genetics of Ovarian Cancer
What to Expect When You Meet With a Genetic Counselor
Colon Cancer Alliance
www.ccalliance.org
C3: Colorectal Cancer Coalition
www.fightcolorectalcancer.org
To find a genetic counselor in your area, ask your doctor or visit the following websites:
National Society of Genetic Counselors
www.nsgc.org
National Cancer Institute: Cancer Genetics Services Directory
www.cancer.gov/search/geneticsservices
