Lynch syndrome (LS) is an inherited genetic condition that increases your risk of developing certain cancers, commonly colorectal cancer or endometrial cancer. If one of your parents has a gene mutation for LS, you have a 50 percent chance of inheriting LS.

Not everyone who inherits LS gene mutations will develop colon or other cancers. LS means that you have a higher risk of developing cancer than the general population. You also have a higher risk for getting cancer at an earlier age.

An LS diagnosis is confirmed by a blood test that detects specific gene mutations. Recent advances in genetics and in cancer treatments have made it possible to identify LS and treat associated cancers earlier and with more success.

It’s projected that up to 1 million people in the United States have LS, but that only 5 percent are now diagnosed. Though not rare, it’s an underdiagnosed condition.

LS is also known as hereditary nonpolyposis colorectal cancer (HNPCC).

Colorectal cancer is the most common cancer associated with LS. Endometrial cancer (cancer of the lining of the uterus) in women is the second most common LS-associated cancer.

If you have LS, your lifetime risk of developing colorectal cancer is 50 percent to 70 percent.

Also, people with LS develop colorectal cancer at a younger age than people without LS. The average age of onset for colorectal cancer in people with LS is mid-40s, which is decades earlier than the average age seen in the general population.

If you’re a woman with LS, your lifetime risk of developing endometrial cancer is 40 percent to 60 percent.

Below are other cancer risks (compared to the general population) associated with gene mutations in the MLH1 and MSH2 chromosomes in people with LS:

  • gastric (6 percent to 13 percent)
  • ovarian (4 percent to 20 percent)
  • urinary tract (0.2 percent to 25 percent)
  • pancreas (0.4 percent to 4 percent)
  • brain (1 percent to 4 percent)
  • small bowel (4 percent to 12)
  • hepatobiliary tract (liver, gallbladder, bile) (0.2 percent to 4 percent)

People with LS can develop more than one type of cancer.

In the early stages of colon cancer, you may not notice any particular symptoms. Symptoms sometimes don’t appear until the cancer has advanced.

Here are some possible symptoms of colon cancer. But note that these symptoms may have other causes.

  • diarrhea, constipation, or other bowel changes that last for more than a few days
  • rectal bleeding or blood in your stool
  • changes in stool color or shape
  • a constant feeling that you need to have a bowel movement
  • excessive gas
  • cramps or abdominal pain
  • fatigue and a feeling of weakness
  • unintended weight loss

If you have changes in your bowel habits, it’s best to see your doctor. The sooner that colon cancer is diagnosed, the easier it is to treat.

The American Cancer Society recommends screening for colon cancer starting at age 45 if you are considered “average risk.” If you have a family history of colon cancer or know you have LS, discuss a screening schedule with your doctor, as you may benefit from starting screening at a younger age.

Colon cancer screening may reveal polyps, precancerous growths that can be removed before they develop into cancers. People with LS may develop polyps earlier than people without LS, but not in greater numbers.

Polyps in people with LS tend to be small and flat. To detect them may require a higher-definition colonoscopy technique.

It took about 100 years before researchers determined the cause of LS.

LS was first identified in 1895, when an American doctor noticed a pattern of cancer deaths in one extended family. He concluded that there might be an inherited predisposition for early cancers in some families.

Several decades later, another American doctor, Henry T. Lynch, documented a pattern of early cancers in families. In 1985, Dr. Lynch called the condition hereditary nonpolyposis colorectal cancer (HNPCC). More recently, it’s been known as LS.

As genetic science and lab techniques advanced in the 1990s, researchers were able to pinpoint the exact mutations on specific chromosomes that are involved with LS.

The genetic mutation

LS-inherited mutations occur on one or more of the genes that normally repair routine DNA mistakes in cell development. These are called mismatch repair genes (MMR).

In LS, these MMR mutations occur on particular chromosomes known as MLH1, MSH2, MSH6, PMS2, and a few others. Mutations on the first three are most common.

Multiple mistakes in DNA repair for people with LS are also called:

  • microsatellite instability
  • loss of MMR protein expression

How the mutation is inherited

If one of your parents has an LS-associated genetic defect, you have a 50 percent chance of inheriting the defect. This is known as an autosomal dominant inheritance pattern.

If one parent has LS, each of your cells will have a damaged copy of the gene and a working copy — one from each parent. If a random (sporadic) mutation causes the functional copy also to become damaged, then the cell will be defective. It will be unable to make DNA repairs. It’s thought that when a cell can’t make DNA repairs, this also causes more random mutations in cells.

Some people with LS may not develop a cancer because their functional copy of the MMR gene doesn’t mutate.

Advances in genetic testing have made it possible to determine with 100 percent specificity whether you have the known mutations for LS.

If you have a family pattern of certain cancers, or if someone in your family has LS, getting tested has definite benefits. This is the case even if you have no cancer symptoms.

Most important: Once you know you have LS, you can get regular screening to catch any cancers early.

Research on LS screening has shown that it’s associated with:

  • 62 percent reduction in colon cancer incidence
  • 65 percent reduction in overall death rates
  • 7-year increase in life expectancy

Most insurance companies cover the majority of the cost of genetic testing when it’s medically necessary, according to the Lynch Syndrome International website. Discuss this with your doctor or genetic counselor, and check with your insurance company.

Some people prefer to pay out-of-pocket for genetic testing because they want their results to be private.

International groups have established guidelines for doctors to decide when to do genetic testing to determine if someone has LS. But the guidelines miss some people who are later found to have LS.

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group recommends screening for LS for all people newly diagnosed with colon cancer. That way, blood relatives can be notified and screened if they have LS, and lives may be saved.

If you don’t have any signs or symptoms of cancer, your initial “treatment” will be regular cancer screening procedures. Discuss a schedule for colonoscopies with your doctor. Each individual case is different.

You may also want to see a genetic counselor to discuss concerns and treatment options for yourself and your family.

The Lynch Syndrome International website refers to people with LS who don’t have cancer as “previvors.”

The statistics on LS cancers show that screening colonoscopies lead to cancers being identified in earlier stages, which have better treatment possibilities. Colonoscopies also are associated with a reduced rate of cancerous tumors.

If you have LS and colon cancer, your treatment may be similar to other people with colon cancer. But colon cancer in some people with LS may be resistant to the usual chemotherapy drugs.

For example, studies show that the 5-fluorouracil immunotherapy drug may not be as effective on colon cancer in people with LS.

New types of treatment are showing promise. A 2018 review noted that monoclonal antibody treatment (pembrolizumab or nivolumab) for advanced colon cancer associated with LS produced 70 percent or greater disease control rates.

In some cases, colon cancer surgery for people with LS may be more extensive. This is because there’s a 16 percent recurrence rate for colon cancer after a partial removal of the colon (colectomy).

Some people with LS may choose to have a preventive colectomy. Discuss your options with your doctor, as each case is different.

Managing LS

Keeping to your prescribed schedule for screening will catch cancer earlier and give you a better prognosis.

It’s recommended that people with LS be monitored with a colonoscopy every one to two years, beginning at ages 20 to 25, or 10 years before the age at which someone in your family was diagnosed with colon cancer.

Women with LS should have an annual gynecological exam. The U.S. Preventative Services Task Force recommends women ages 21 to 29 get a Pap test every three years. Women ages 30 to 65 can opt to continue this schedule or get an HPV test every five years, on its own or together with a Pap test.

Prevention measures

Studies indicate that some environmental factors may have an effect on whether a person with LS will develop colon cancer or another form of cancer. Risks include:

  • cigarette smoking
  • higher body mass index (BMI)
  • high intake of snack foods

Following are a few general rules for cancer prevention:

  • Don’t smoke.
  • Maintain a healthy weight.
  • Eat a healthy diet.
  • Get regular exercise.

In addition to these prevention measures, talk to your doctor about taking aspirin regularly. Studies have found that taking 600 milligrams of aspirin per day for two years or more reduced the risk of LS-related colon cancer by more than 50 percent.

For women, there’s evidence that using oral contraceptives can reduce your risk of endometrial cancer.

The understanding of LS has greatly advanced in the last 20 years, and progress continues to be made.

Today a genetic analysis of your particular LS-related MMR gene defects can help your doctor design a screening and treatment plan for your particular case. There’s promising new research in immune-based LS treatment, so be sure to discuss LS treatment developments with your doctor

Regular screening may not prevent colon cancer, but it can find it and treat it earlier. A 2015 review of screening results for people with LS concluded that early detection and treatment of colon cancer was associated with “excellent survival.”

An earlier controlled study that looked at the effect of screening for colon cancer in people with LS found that over 15 years, screening every 3 years:

  • more than halved the risk of colon cancer
  • prevented colon cancer deaths
  • cut overall mortality by 65 percent

If you have LS, or if you’d like to have genetic testing to find out whether you have LS, you may want to check out the website resources of Lynch Syndrome International. There’s also a new Lynch Syndrome Screening Network that lists all the U.S. hospitals and clinics where genetic testing for LS is available.