Gene Mutation MSH2 and Cancer Risk
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Gene Mutation MSH2 and Cancer Risk

Gene Mutation MSH2 and Cancer Risk
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Updated on August 23, 2022
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If You Carry an MSH2 Gene Mutation, What Cancers Are You at Risk For?

Having an error, or mutation, in one copy of the MSH2 gene causes Lynch syndrome, which raises a person’s risk for developing:

  • Colorectal cancer
  • Endometrial cancer
  • Ovarian cancer
  • Stomach cancer
  • Small intestine cancer
  • Liver cancer
  • Gallbladder duct cancer
  • Upper urinary tract cancer
  • Brain cancer

Research also shows that Lynch syndrome increases a woman’s risk of having breast cancer.

About 1 in 440 people in the United States carries a gene mutation that causes Lynch syndrome. In addition to MSH2, researchers have identified four other gene alterations that are linked to the disorder. (1)

About 40 percent of Lynch syndrome cases related to a gene mutation are associated with defects in the MSH2 gene.

Certain mutations in the MSH2 gene can cause another form of Lynch syndrome, known as Muir-Torre syndrome. People with this condition have an increased risk of developing colorectal cancer and rare tumors on the skin. (2)

How Does MSH2 Increase Your Risk for Cancer?

The MSH2 gene provides directions for making the MSH2 protein, which helps repair errors made when DNA is copied prior to cell division.

The MSH2 protein combines with one of two other proteins — either MSH6 or MSH3 — to form a protein complex. This complex finds locations on DNA where errors occurred during replication. Then another group of proteins — the MLH1-PMS2 complex — fixes the errors.

MSH2 is part of a set of genes known as the mismatch repair (MMR) genes. (2)

Can You Be Tested for MSH2?

Yes, you can take a genetic test to identify an MSH2 mutation.

You might consider testing if your relatives have gene mutations, you develop an MSH2-related cancer at a young age, you have a family history of MSH2-related cancers, or you have other risk factors.

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 expert can explain the benefits and drawbacks of testing, while helping you interpret your results.

Why Is It Important to Know if You Are at Risk for MSH2?

Finding out you have an MSH2 gene mutation can be useful information for your family members. It can also help you better understand your cancer risk.

Men and women with an MSH2 mutation have between a 52 and 82 percent chance of developing colon or rectal cancer in their lifetime. Women with the defect have between a 25 and 60 percent lifetime risk for endometrial cancer and between a 4 and 13 percent lifetime risk for ovarian cancer. (3)

If you have an MSH2 alteration, there’s a fifty-fifty chance that you’ll pass it on to each of your children. (4)

History of the MSH2 Gene: When Was It First Discovered?

In 1967, American physician Henry Lynch, MD, first described Lynch syndrome, which is also called “hereditary nonpolyposis colorectal cancer.”

Scientists discovered that mutations in the MSH2 gene were associated with Lynch syndrome in 1993. (5)

What Do You Do if You Test Positive for an MSH2 Mutation?

If you have an MSH2 mutation, your healthcare provider will probably recommend earlier and more frequent cancer screening tests.

The Facing Our Risk of Cancer Empowered (FORCE) organization gives 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
  • Breast cancer screening based on family history
  • Annual pelvic examination, pelvic ultrasound, and endometrial biopsy for women from age 30 to 35

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 two to five years before the earliest colon cancer diagnosis in the family)
  • Aspirin to lower the risk of colon cancer
  • Genetic screening for other cancers based on family history, as directed by a doctor
  • An annual urinalysis starting at age 30 to 35 if you have a family history of urothelial cancer or an MSH2 mutation
  • An annual physical, total body skin exam, and neurological exam starting at age 25 to 30

Talk to your doctor about an individualized screening approach. (6)

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Conor Steuer, MD

Medical Reviewer
Castle Connolly Top Doctor

Conor E. Steuer, MD, is medical oncologist specializing in the care of aerodigestive cancers, mesothelioma, and thymic malignancies and an assistant professor in the department of hematology and medical oncology at the Emory University School of Medicine in Atlanta. He joined the clinical staff at Emory's Winship Cancer Institute as a practicing physician in July 2015. He currently serves as chair of the Lung and Aerodigestive Malignancies Working Group and is a member of the Discovery and Developmental Therapeutics Research Program at Winship.

Dr. Steuer received his medical degree from the New York University School of Medicine in 2009. He completed his postdoctoral training as a fellow in the department of hematology and medical oncology at the Emory University School of Medicine, where he was chief fellow in his final year.

He has been active in research including in clinical trial development, database analyses, and investigation of molecular biomarkers. He is interested in investigating the molecular biology and genomics of thoracic and head and neck tumors in order to be able to further the care of these patient populations. Additionally, he has taken an interest in utilizing national databases to perform clinical outcomes research, as well as further investigate rare forms of thoracic cancers.

Steuer's work has been published in many leading journals, such as Cancer, the Journal of Thoracic Oncology, and Lung Cancer, and has been presented at multiple international conferences.

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Julie Lynn Marks

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Julie Marks is a freelance writer with more than 20 years of experience covering health, lifestyle, and science topics. In addition to writing for Everyday Health, her work has been featured in WebMD, SELF, Healthline, A&E, Psych Central, Verywell Health, and more. Her goal is to compose helpful articles that readers can easily understand and use to improve their well-being. She is passionate about healthy living and delivering important medical information through her writing.

Prior to her freelance career, Marks was a supervising producer of medical programming for Ivanhoe Broadcast News. She is a Telly award winner and Freddie award finalist. When she’s not writing, she enjoys spending time with her husband and four children, traveling, and cheering on the UCF Knights.

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EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Additional Sources
  1. Two New Breast Cancer Genes Emerge from Study of Lynch Syndrome. Columbia University Irving Medical Center. January 18, 2018.
  2. MSH2 Gene. MedlinePlus. April 1, 2020.
  3. Q&A: Understanding and Managing Lynch Syndrome. MD Anderson Cancer Center. January 5, 2010.
  4. Understanding Your Positive MSH2 Genetic Test Result. Ambry Genetics.
  5. Boland CR, Lynch HT. The History of Lynch Syndrome. Familial Cancer. June 2013.
  6. Lynch Syndrome. American Society of Clinical Oncology. September 2021.

Additional Source