What is Lynch Syndrome?
Lynch Syndrome is the most common form of hereditary colorectal cancer affecting more than 1.2 million people in the United States.
Lynch Syndrome Cancers
Patients with Lynch syndrome carry an increased risk for certain cancers. Unfortunately, an estimated 95% of Lynch syndrome cases are undiagnosed.
If you have Lynch syndrome, your risk of several cancers is higher compared to others without the same mutated gene. There are several Lynch syndrome-associated cancers. Your risk for each cancer type will depend on your mutated gene, as well as if you’re biologically male or female.
Colon and Rectal Cancers
Up to 3-5% of all colorectal cancer is due to Lynch syndrome. People with Lynch syndrome have a 15-80% lifetime risk of developing colorectal cancer (compared to a 5% risk for people with average risk).
The average age of a colorectal cancer diagnosis for someone with Lynch syndrome can occur decades below the screening age. Lynch syndrome is a common cause of colorectal cancer in young adults.
Colorectal cancer in Lynch syndrome patients may form quicker than average-risk patients, and colorectal cancer screening will need to occur much more frequently for Lynch patients.
Endometrial (Uterine) Cancer
Women with Lynch syndrome carry an elevated risk of developing endometrial cancer. Depending on the mutated gene, there is a 14-71% lifetime risk. To prevent uterine cancer, doctors may recommend a hysterectomy if there are no plans for childbearing or if a woman is past the age for childbearing.
Women with Lynch syndrome carry a 4-24% chance of developing ovarian cancer. To prevent ovarian cancer, doctors may recommend an oophorectomy (ovary removal) if there are no plans for childbearing or if a woman is past the age for childbearing.
Men and women with Lynch syndrome carry a 1-13% lifetime risk of developing stomach cancer.
Breast and Prostate Cancers
There are differing opinions on whether breast cancers and prostate cancers are part of Lynch syndrome’s associated cancers. However, studies show that Lynch patients may carry an elevated risk for these cancers.
Women with Lynch carry a slightly increased risk of breast cancer compared to others in the population (as high as 18% for Lynch patients compared with 12% for average-risk women).
Men with Lynch carry an elevated risk for prostate cancer (as high as 30% for Lynch patients compared to 16% for average-risk men).
Other Related Cancers
Lynch syndrome patients face an increased risk for several cancers compared to an average-risk person without a hereditary cancer syndrome. If any of the Lynch-associated cancers run in your family, it’s important to let your geneticist know.
- Upper urinary tract cancer (up to 28%)
- Skin cancer (up to 9%)
- Pancreatic cancer (up to 6%)
- Small intestine cancer (up to 6%)
- Bladder (up to 6%)
- Hepatobiliary tract cancer (up to 4%)
- Brain/central nervous system cancer (up to 3%)
- Kidney cancer (up to 3%)
Lynch Syndrome Genes
The Lynch syndrome genes are in a class of genes called mismatch repair (MMR). MMR genes work like “spell checkers.” Every time your body needs to make a new cell (which happens frequently), it makes an exact copy of your genetic material.
There are four “repair” genes, or MMR genes, that can be involved with Lynch syndrome, and one gene that can indirectly cause it.
The gene EPCAM (formerly TACSTD1) can ‘turn off’ the MSH2 gene, therefore leading to this cancer syndrome.
About MMR Genes
The MMR genes “spell check” the new copy of DNA to identify any mistakes that were made while it was being copied, and then the genes repair those mistakes. If the MMR genes are mutated and not working properly, these mistakes cannot be repaired, and the new DNA cells will have an abnormal copy of its genetic material.
When any one cell accumulates enough mistakes in its genetic material, it may start to grow out of control and not die when it should. That cell can become a cancer.
Other Types of Hereditary Colorectal Cancers
Lynch syndrome is the most common form of hereditary colorectal cancer syndromes. The second-most common is familial adenomatous polyposis (FAP). Read our Genetics Mini Magazine to learn about all types of hereditary colorectal cancers.
Muir-Torre syndrome is a form of Lynch syndrome that can bring an increased risk of skin growths and cancers in addition to Lynch-related cancers.
Lynch Syndrome Testing
How and when you get tested for Lynch syndrome will depend on if you have or have not been diagnosed with cancer. Most people diagnosed with Lynch syndrome inherited the mutation from one of their parents, and each of their children carry a 50% chance of also inheriting the mutation.
Typically, your results will come back:
- Positive/Clinically significant: you have a genetic mutation
- Variant of uncertain (or unknown) significance (VUS): there’s a variation in your gene, but it’s unknown if it leads to increased cancer risk
- Negative/No known mutation: the genes tested did not show a mutation
Testing Cancer Patients for Lynch
Many institutions now perform a screening test on all colorectal cancers and endometrial (uterine) tumors at the time of surgery. If you’re not sure if this test was done, ask your oncologist. If your surgery was not too long ago, it’s likely the test can still be performed if it wasn’t done. Most hospitals do one of these two screening tests, if not both.
Microsatellite Instability (MSI)
An MSI screening test looks for changes in the DNA sequence by comparing normal tissue and tumor tissue. Defects in the MMR genes result in an increased accumulation of DNA errors, and stretches of DNA called microsatellites are especially prone to these errors.
77-89% of Lynch-related tumors show MSI, but 10-15% of sporadic tumors also show it.
Given that both Lynch and sporadic tumors can show MSI, additional testing is needed to determine if it is truly Lynch syndrome. MSI testing will also identify if a tumor is MSI-H.
Learn more about MSI vs MSS tumors.
An immunohistochemistry (IHC) test looks for missing proteins in tumor cells. The premise behind the test is that if the MMR genes are working properly, their protein products should be present in the tumor. However, if there is a mutation in one of the Lynch syndrome MMR genes, that gene’s protein will be absent in the tumor.
83-90% of Lynch-related tumors and 20% of sporadic tumors have at least one of these proteins absent.
IHC testing looks to see if there are missing proteins, which are made by MMR genes. If the test is abnormal, you are more likely to have Lynch syndrome. This would need to be determined by doing genetic testing for Lynch syndrome genes. If the test is normal, you are less likely to have Lynch syndrome, but it cannot be ruled out entirely.
Testing for Lynch if You Don’t Have Cancer
If you have not been diagnosed with cancer, ask your family members who have about their genetic testing results. This may influence your next steps. It’s important to work with a genetic counselor who can help you understand the process. To find one near you, search the National Society of Genetic Counselors.
Your family history may give you clues that Lynch syndrome runs in your family and you would benefit from getting tested:
- There are multiple generations on one side of the family (great-grandparent, grandparent, parent, aunt/uncle, child) with a Lynch-associated cancer
- There may be “clustering” of certain cancers in the family and higher risk of certain cancers
- Individuals in the family may have more than one cancer
Many insurance plans and some genetic test providers will offer genetic testing if there’s been a diagnosis of Lynch syndrome in the family. It’s important to speak with a genetic counselor about your testing options.
Should You Use 23andMe for Lynch Syndrome Testing?
Although 23andMe has brought some awareness to hereditary colorectal cancer, it does not offer any tests that look for Lynch genes. The test looks for the MUYTH gene, which is associated with colorectal cancer. Currently 23andMe, along with other direct consumer testing options, could give a person a false sense of their overall colorectal cancer risk due to hereditary colorectal polyps/cancer genes. For more information, read our blog about using 23andMe’s test for colorectal cancer risk.
Genetic Testing Costs
Costs of genetic testing can vary depending on several factors including insurance plan, personal cancer history, family health history, and the genetic test provider. Learn more about genetic testing costs for Lynch syndrome.
Can you have Lynch Syndrome if you Don’t Have a Family History?
Although it’s uncommon, it is possible to carry a Lynch syndrome gene mutation and not have a family history. In these cases, the patient with Lynch is considered “de novo,” or the first in the family line to carry the mutation.
Where Did Lynch Syndrome Come From?
Dr. Henry Lynch, who devoted his career to studying nonpolyposis colorectal cancer, discovered a strain of genes that led to an increased risk of certain cancers, with colorectal cancer carrying the greatest risk. His discoveries have led to increased awareness and prevention of many cancers.
Lynch Syndrome vs HNPCC
Hereditary nonpolyposis colorectal cancer, or HNPCC, is often called Lynch syndrome. Although the two hereditary conditions are very similar, what defines them is what makes them different. Lynch-related cancers are defined by mutations in a gene, whereas family history and other criteria determine what is considered HNPCC. Learn more about HNPCC vs. Lynch syndrome from the Cleveland Clinic.
Does Everyone with Lynch Syndrome Get Cancer?
The diagnosis of Lynch syndrome can be scary, but knowledge is power! The sooner you know if you carry a Lynch syndrome gene, the more aggressive you can be to prevent cancer. Not everyone who is diagnosed with Lynch syndrome will get cancer, but everyone with Lynch syndrome carries a higher risk for certain cancers.
“Previvor” is the term that describes someone with Lynch syndrome who has NOT been diagnosed with cancer. If you have Lynch syndrome, it is critical to notify all of your doctors so you can follow an aggressive cancer prevention plan. Read more about previvors in Beyond Blue.
I Have Lynch Syndrome – Now What?
There are many resources available to help you! It’s important to first understand your cancer screening and prevention guidelines.
Lynch Syndrome Screening Guidelines
The American Society of Clinical Oncology recommends these general screening and risk-reduction guidelines for Lynch syndrome patients:
- 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)
- Upper endoscopy: Every three to five years, in addition to testing for Helicobacter pylori infection at a baseline exam with treatment if positive
- Total body skin examination: Yearly
- Pelvic examination/pelvic ultrasound/endometrial biopsy (women): Yearly from age 30 to 35
Screening for other cancers associated with Lynch syndrome may be recommended depending on your family history, though the effectiveness of such screening remains unproven.
Consideration of daily aspirin, which may be linked to a reduced risk of colorectal cancer and possibly other cancers in individuals with Lynch syndrome. Before taking aspirin, discuss with your doctor.
Lynch Syndrome Treatment
Recent studies suggest that immunotherapy may be an effective approach to treat colorectal cancer with MSI, which is often found in Lynch syndrome patients. Knowing your MSI status could drastically change your treatment plan.
Lynch Syndrome Support
It’s important to have HOPE, even if you test positive for Lynch syndrome. Many of our relentless champions are living with Lynch syndrome, both as survivors and previvors! For more support and information about Lynch syndrome, check out:
- AliveAndKickn – a Lynch syndrome hereditary cancer advocacy organization
- Lynch Syndrome International – raising awareness and providing education
- Lynchville by Colontown – a Facebook group for survivors and previvors with Lynch
- ThinkGenetic – Answers to common questions about Lynch syndrome
More Lynch Syndrome Resources
If you’re living with Lynch syndrome, you’re not alone! We have many resources to help you. A popular resource among Lynch syndrome patients is our webinar on healthy lifestyle choices that prevent a colorectal cancer recurrence.
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