Lynch Syndrome: Cancer Risks, Screening and Family Testing
Lynch syndrome is an inherited condition that raises the risk of colorectal, endometrial and other cancers, often at younger ages. About 1 in 279 people carry it. Regular colonoscopy, starting as early as age 20 to 25 and repeated every 1 to 3 years, lowers the risk of colorectal cancer and of dying from it. Each child or sibling of a carrier has about a 50% chance of having the same gene change.
Finding out you have Lynch syndrome can be frightening. It does not mean you have cancer or that you will get it. It means your risk is higher, and that screening and prevention can make a real difference. It used to be called hereditary non-polyposis colorectal cancer, or HNPCC.
What causes it
Our cells use mismatch repair genes to fix errors that happen when DNA is copied. Lynch syndrome is caused by an inherited change in one of these genes: MLH1, MSH2, MSH6 or PMS2. A fifth gene, EPCAM, is not a repair gene, but changes in it can switch off MSH2.
When repair fails, errors build up in cells, and over time this can lead to cancer. One changed copy of the gene is enough to raise your risk. Not everyone with Lynch syndrome gets cancer.
Lynch syndrome causes about 3% of colorectal cancers and at least 2.3% of endometrial cancers. It is the most common inherited cause of colorectal cancer.
Cancer risks by gene
Your risk depends on which gene is changed. These figures come from the National Cancer Institute (NCI) summary of the research. Estimates vary between studies, and older ones may run high, so read them as ranges and not as your personal number.
| Gene | Colorectal cancer, lifetime | Endometrial cancer, lifetime |
|---|---|---|
| MLH1 | 41% to 50% | 34% to 54% |
| MSH2 | 35% to 56% | 21% to 51% |
| MSH6 | 10% to 22% | 26% by age 70 |
| PMS2 | 11% to 20% by age 70 | 15% by age 70 |
MLH1 and MSH2 generally carry the highest risks. MSH6 and PMS2 carry lower risks, which is why their screening starts later.
Other cancers are also more common. NCI gives these risks by age 70 across Lynch syndrome:
- Ovarian cancer: 3.4% to 22%, compared with 1.3% in the general population
- Stomach cancer: 0.2% to 13%, compared with less than 1%
- Urinary tract cancers: 0.2% to 25.5%, compared with less than 1%
The American Cancer Society (ACS) also lists small intestine, pancreatic, kidney, brain, skin, breast, prostate, ureter and bile duct cancers. Some people develop more than one cancer. Cancers tied to Lynch syndrome often appear young, frequently before age 50, and colon cancers are often on the right side. People usually have only a few polyps, which is one reason the condition can be missed.
Screening schedule
This table reflects NCCN guidelines as summarized by NCI. NCCN is a US group of cancer centers. Other countries' guidelines differ, and yours may change with your gene and family history. A genetics team or gastroenterologist should set your exact plan.
| Test | Who | Start | Repeat |
|---|---|---|---|
| Colonoscopy | MLH1, MSH2 (and EPCAM) | Age 20 to 25, or 2 to 5 years before the earliest colorectal cancer in the family if that was before 25 | Every 1 to 2 years |
| Colonoscopy | MSH6, PMS2 | Age 30 to 35, or 2 to 5 years before the earliest family case if that was before 30 | Every 1 to 3 years |
| Upper endoscopy (a camera into the stomach) | People with Lynch syndrome | Age 30 to 40, sometimes earlier with risk factors | Every 2 to 4 years |
| Endometrial biopsy (a sample of the uterine lining) | Women who still have a uterus | Can be considered from age 30 to 35 | Every 1 to 2 years |
| Urinalysis | Can be considered with a family history of urinary tract cancer or an MSH2 change, especially in men | Age 30 to 35 | Yearly |
NCCN does not recommend routine ovarian cancer screening in Lynch syndrome. A transvaginal ultrasound is not recommended as a screening test before menopause.
Colonoscopy works. NCI reports that having one every 1 to 2 years, and up to 3 years in one study, reduces colorectal cancer cases and deaths. It does not remove all the risk. Some people still get colorectal cancer despite regular screening. Those cancers should be found earlier, which is why keeping appointments matters.
See your doctor promptly, even if your last screen was normal, if you have: blood in your stool; a change in bowel habits that lasts; unexplained weight loss; bleeding between periods or after menopause; or blood in your urine.
Lowering your risk
Aspirin
NCI says guidelines consistently recommend that people with Lynch syndrome consider taking aspirin daily. In the CAPP2 trial, 600 mg a day lowered colorectal cancer risk by about a third after more than 10 years of follow-up. About 24 carriers would need to be treated to prevent one cancer. Protection appeared about 5 years after starting.
That is a high dose, and aspirin can cause bleeding. It may not be safe in pregnancy. Lower doses are being studied. Talk with your doctor before starting, because the right dose depends on your health.
Risk-reducing surgery
Removing the uterus (hysterectomy) and the ovaries and fallopian tubes is an effective way to prevent endometrial and ovarian cancer. In a study of 315 women, none who had the surgery got these cancers, while 33% of those who did not get it developed endometrial cancer and 5.5% developed ovarian cancer. The study looked back at past records, so it may overstate the benefit.
This surgery ends fertility, and removing ovaries before natural menopause causes early menopause. Timing is personal. It usually depends on your gene, age and plans for children. One modeling study found annual screening from age 30 followed by surgery at age 40 was the most effective approach.
Healthy habits
ACS suggests staying at a healthy weight, being active and avoiding or limiting alcohol. These do not replace screening. See our page on cancer surgery for general information about preventive operations.
How it is diagnosed
There are two routes. Doctors often find it after a cancer is tested, or because of family history.
- Tumor testing. NCCN supports testing all colorectal and endometrial cancers for signs of faulty repair. The tests are called MSI (microsatellite instability) and IHC (immunohistochemistry). An abnormal result raises the possibility of Lynch syndrome but does not prove it, because not everyone with MSI has the condition.
- Genetic testing. A lab test looks for an inherited change. This is what confirms the diagnosis. Genetic testing is best done with a genetic counselor, who can explain benefits, limits and uncertain results.
NCI advises considering genetic counseling if you or a relative had colorectal cancer before age 50, if a relative has a known gene change, or if several relatives had related cancers, especially at young ages. When possible, testing should start with a family member who has had cancer.
The result can affect treatment too. Pembrolizumab and nivolumab have shown good results in metastatic colorectal cancer with faulty mismatch repair. See immunotherapy for more.
What it means for your family
Lynch syndrome can pass from either parent. Each parent, child, brother and sister of a carrier has about a 50% chance of having the same change. Men and women are equally likely to inherit it. It does not skip a person: someone who does not have the change cannot pass it on.
A relative with the known family gene change can have a simple test for it. This is called cascade testing, and it can give a clear answer. Relatives who test negative do not have the family's Lynch change, and can ask their doctor what screening they need. Those who test positive can begin early screening before cancer develops.
Telling relatives can be hard. A genetic counselor can help you plan what to say. Not everyone will want to know. If relatives decline testing, ACS says they may still choose early screening.
Insurance. In the US, a law called GINA bars health insurers and employers from discriminating based on genetic information. It does not cover life, disability or long-term care insurance, and it does not cover members of the military. Some states have added protections. Consider this before testing.
Frequently asked questions
Is Lynch syndrome hereditary?
Yes. It is passed down from a parent. Each child of a carrier has about a 50% chance of inheriting it. Brothers, sisters and parents of a carrier may also have it, so close relatives should consider testing.
How often should people with Lynch syndrome have a colonoscopy?
Under NCCN guidelines, usually every 1 to 2 years from age 20 to 25 for MLH1 or MSH2 changes, and every 1 to 3 years from age 30 to 35 for MSH6 or PMS2 changes. Your doctor may start earlier based on your family.
Will I definitely get cancer if I have Lynch syndrome?
No. Not everyone with Lynch syndrome gets cancer, and the risk varies by gene. Regular screening can find problems early, and colonoscopy can remove polyps before they turn into cancer.
What is the life expectancy with Lynch syndrome?
We could not find one figure that applies to everyone. Outlook depends on whether cancer develops, what kind, and how early it is found. Regular colonoscopy has been shown to reduce colorectal cancer deaths.
Should I take aspirin if I have Lynch syndrome?
Ask your doctor. Guidelines consistently say people with Lynch syndrome should consider daily aspirin, and a large trial showed lower colorectal cancer risk at 600 mg a day. The best dose is still being studied and aspirin can cause bleeding.
Can I have Lynch syndrome with no family history of cancer?
It is possible. Not everyone with the gene change gets cancer, so a family pattern can be hard to see. If you have a cancer that suggests it, ask about genetic counseling.
Does insurance cover Lynch syndrome testing?
Coverage varies by plan. Ask your insurer and a genetic counselor before testing. GINA protects you from health insurance and job discrimination, but not in life, disability or long-term care insurance.
Sources
- National Cancer Institute: Genetics of Colorectal Cancer (PDQ), Health Professional Version
- American Cancer Society: Lynch Syndrome
- American Cancer Society: Colorectal Cancer Risk Factors
- MedlinePlus Genetics: Lynch syndrome
- Colonoscopic surveillance in Lynch syndrome: guidelines in perspective
- National Cancer Institute: Genetic Testing for Inherited Cancer Risk
This page is general information, not medical advice. Your care team knows your situation and should guide your decisions.