Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC) syndrome is caused by mutations (or changes) in one of five known genes: MLH1, MSH2, MSH6, PMS2, and EPCAM. Seeing any of the following in a family could increase the chance for Lynch syndrome:
Mutations that cause Lynch syndrome are inherited in an autosomal dominant pattern, meaning that children of someone with Lynch syndrome each have a 50% chance to also have Lynch syndrome and the related increased risks for cancer. Women and men both have the Lynch syndrome genes and have the same chances to inherit and pass down mutations in these genes, therefore both sides of the family are important to look at when trying to determine if someone has a higher chance to have Lynch syndrome.
|Cancer type||Risk in the |
|Risk in Lynch syndrome|
|Colorectal||5.5%||Up to 80%|
|Uterine/Endometrial||2.7%||Up to 60%|
|Ovarian||1.2%||Up to 24%|
|Stomach||<1%||Up to 13%|
|Small intestine||<1%||Up to 6%|
|Urinary tract (specifically renal pelvic type)||<1%||Up to 7%|
|Hepatobiliary tract||<1%||Up to 4%|
|Pancreatic||<1%||Up to 6%|
|Brain cancer||<1%||Up to 3%|
|Skin (specifically sebaceous |
|<1%||Up to 9%|
It is important to remember that there are 5 genes that are known to cause Lynch syndrome and each of these genes have their own unique cancer risk numbers. The MLH1, MSH2, and EPCAM genes are associated with a higher risk of cancers (as described in the above table), while the MSH6 and PMS2 genes are still associated with an increased risk for cancer, just not as high as with MLH1, MSH2, and EPCAM. All individuals who have Lynch syndrome should be offered additional surveillance and screening regardless of which of the five genes is causing their Lynch syndrome.
Genetic testing for mutations that cause Lynch syndrome has been available for many years, and the testing methods have changed and improved over time. There are several different ways to approach to testing in these genes, depending on the history and any prior testing that may have been done. Different approaches include:
This testing is different from other types of genetic tests because it is done specifically on a person’s cancer/tumor. Some hospitals complete this testing on all patients diagnosed with colon or uterine cancer as part of their treatment, while other facilities do not. The IHC test for Lynch syndrome (also called mismatch repair deficiency) is a screening test, meaning that it cannot tell us with 100% certainty whether or not someone has Lynch syndrome. It also may not find all patients that truly have Lynch syndrome. More commonly, positive results from IHC screening end up being a false positive, meaning that the person’s tumor looks like Lynch syndrome, but this is later ruled out by genetic testing. Individuals who have an abnormal IHC screening test should be referred to speak with a genetic counselor to discuss the results and help determine if genetic testing for Lynch syndrome is indicated and something that the patient wants to do. Many patients do not know if an IHC screening test was performed on their cancer, but you can ask your doctor about this information.
Other than someone’s personal history of cancer, another piece of information that we can use to help determine if someone is at a higher risk to have Lynch syndrome is your family history. The National Comprehensive Cancer Network (NCCN) is a group of medical professionals that regularly meet to look over any updates in research studies and determine recommendations for who should be considered at a higher risk for one of these gene mutations, and thus should be offered genetic testing.
Cancers that are associated with Lynch syndrome include: colon cancer, uterine cancer, ovarian cancer, pancreatic cancer, stomach cancer, small intestinal cancer, hepatobiliary cancer, brain cancer (specifically glioblastoma), urinary tract cancer (specifically renal pelvic type), and sebaceous skin tumors/cancer.
You should consider genetic counseling and possibly genetic testing if you see these cancers within your family history (make sure to include yourself in your family history if you have been diagnosed with cancer), specifically if you see:
These are some loose guidelines for who may be at an increased risk, but a medical professional, such as a genetic counselor, will be able to meet with you to further flush out your family history and help determine if you meet criteria for genetic testing.
If you are tested and found to have Lynch syndrome, it is recommended to discuss your management plan with your healthcare team, and if available, to seek consultation through a specialized high-risk clinic. General recommendations are included here based on the updated guidelines of the NCCN, but may be tailored to your specific medical and family history.
All individuals with Lynch syndrome should have a colonoscopy every 1-2 years to look for colon polyps which may grow into colorectal cancer. This screening should start around age 20-25. The good news is that this screening for colon cancer is highly effective in reducing the chance that someone would develop colon cancer and reduces the severity of colon cancer.
An endoscopy (EGD) to look at the stomach and duodenum (the first part of the small intestine immediately beyond the stomach) may be considered for those who have a family history of stomach or small intestinal cancer or have other risk factors for these cancers (i.e. Asian descent).
Women at increased risk for uterine and ovarian cancer due to having Lynch syndrome are encouraged to consider prophylactic (preventative) removal of the uterus, ovaries, and fallopian tubes once they are certain they would not like any future pregnancies. For women who do not elect preventive surgery, screening for these cancers may include biopsies of the uterus, checking CA-125 blood levels to screen for ovarian cancer, and transvaginal ultrasound. However, these screenings have not proven to be effective and are not recommended by many medical organizations.
In families with Lynch syndrome and a history of pancreatic cancer, individualized screening may be offered based on the history, but no specific guidelines currently exist.
An annual urine test can be considered to screen for urinary tract cancers starting around age 30-35.
Individuals with Lynch syndrome should have regular physical exams with primary cancer physician including a neurological evaluation.
A Guide for Patients and Their Families (from the Center for Disease Control)
Hereditary Colon Cancer Takes Guts (A Patient’s Guide to Lynch Syndrome)