Gene Mutation MLH1 and Cancer Risk

MLH1 is a gene that helps repair damaged DNA.

An error, or mutation, in one copy of the MLH1 gene is one of the causes of Lynch syndrome, an inherited disorder that raises a person’s risk of developing colorectal cancer and endometrial cancer.

Lynch syndrome can also increase your chances of having:

• Ovarian cancer
• Stomach cancer
• Small intestine cancer
• Liver cancer
• Gallbladder duct cancer
• Upper urinary tract cancer
• Brain cancer (1)

Additionally, recent research shows Lynch syndrome raises a woman’s risk of having breast cancer. (2)

About 1 in 440 Americans carries a gene mutation that causes Lynch syndrome. (2)

Roughly one-half of all cases of Lynch syndrome with an identified gene mutation are associated with the MLH1 gene. (1)

In addition to MLH1, scientists have identified four other gene alterations that have been linked to Lynch syndrome. (2)

Some MLH1 mutations can cause a variation of Lynch syndrome, known as Turcot syndrome. This disorder increases a person’s risk of colorectal cancer and glioblastoma (a type of brain tumor).

Mutations in the MLH1 gene can also cause another form of Lynch syndrome, known as Muir-Torre syndrome. People with this condition have a higher risk of developing colorectal cancer and rare skin tumors. (1)

MLH1 gives instructions for making the MLH1 protein that helps fix errors that are made when DNA is copied before cell division.

The MLH1 protein works with another protein called PMS2 to form a complex, which essentially directs the activities of other proteins that repair DNA errors.

MLH1 is part of a set of genes known as the mismatch repair (MMR) genes. (1)

Yes, genetic testing is available to identify a MLH1 mutation.

You may consider testing if relatives have gene mutations, you develop a MLH1-related cancer, you have a family history of MLH1-related cancer, or you have other risk factors.

To take the test, you’ll be asked to provide a blood or saliva sample that’s analyzed in the lab.

It’s a good idea to talk to a genetic counselor if you’re considering testing. This professional can explain the pros and cons of testing and assist you in interpreting your results. (3)

Identifying an MLH1 gene mutation can help you better assess your cancer risk. It’s also valuable information for your family members.

If you have an MLH1 mutation, you have a fifty-fifty chance of passing it on to your children. (3)

Studies show that men and women with an MLH1 mutation have between a 46 and 61 percent risk of developing colon or rectal cancer during their lifetime. Women with the defect have between a 34 and 54 percent chance of having endometrial cancer in their lifetime. The lifetime risk for ovarian cancer is between 4 and 20 percent. (4)

Lynch syndrome, also sometimes called hereditary nonpolyposis colorectal cancer, was first recognized in medical literature by American physician Henry Lynch in 1967.

Scientists reported mutations in the MLH1 gene in 1994. (5)

If you test positive for a MLH1 mutation, your doctor will probably recommend earlier and more frequent cancer screenings.

The National Comprehensive Cancer Network (NCCN) provides guidelines for people with Lynch syndrome, which include the following:

For Women

Women should consider:

• Risk-reducing surgery to remove the ovaries and uterus after childbearing is complete
• An endometrial biopsy every one to two years
• Breast cancer screening based on family history

It’s also important that women report abnormal gynecological symptoms, such as unusual vaginal bleeding, abdominal pain, or bloating, to their doctor.

For Men and Women

Men and women should consider:

• A colonoscopy every one to two years starting at age 20 to 25 (or every two to five years before the earliest colon cancer diagnosis in the family)
• Aspirin to lower the risk of colon cancer
• Gastric cancer screening via an endoscopic procedure every three to five years starting at age 40 if there’s a family history of gastric cancer or Asian ancestry (If gastric screening is performed, consider testing for H. pylori, a bacteria associated with inflammation and stomach ulcers.)
• A annual urinalysis starting at age 30 to 35 if you have a family history of urothelial cancer or a MSH2 mutation
• An annual physical and neurological exam starting at age 25 to 30

Talk to your doctor about all your preventive screening options. (6)