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PMS2 gene-Lynch syndrome

PMS2 gene-Lynch syndrome

Men and women with a mutation in PMS2 have an approximate 15-20% lifetime risk for colorectal cancer and 6% lifetime risk for other Lynch syndrome associated cancers.  Women have an additional 15% lifetime risk for endometrial cancer.  Lynch syndrome-associated cancers include cancer of the urinary tract, ovary, stomach, small intestine, hepatobiliary tract, skin, and brain.  Several hundred mutations in the PMS2 gene that predispose people to colorectal, endometrial and other Lynch syndrome-associated cancers have been found. These mutations may cause the production of an abnormally short or inactivated PMS2 protein that cannot perform its normal function. When the PMS2 protein is absent or ineffective, the number of mistakes that are left unrepaired during cell division increases substantially. If the cells continue to divide, errors accumulate in DNA; the cells become unable to function properly and may form a tumor in the colon, endometrium or another part of the body.


Mutations in PMS2 are inherited in an autosomal dominant manner, meaning each first degree relative (parent, child, and sibling) of an individual with this condition has a 50% chance of inheriting the disease causing mutation.

Testing Family:

This information is very important for relatives, because some of them may also have the PMS2 mutation, and they could use this information to help prevent cancer for themselves or their children.

Testing of family members for the PMS2 mutation is also important for reproductive planning. If a family member has a PMS2 mutation, and in the rare circumstance that their partner also has a PMS2 mutation, each of their children has a 25% chance of inheriting two PMS2 mutations, one from each parent, which causes Constitutional Mismatch Repair Deficiency (CMMRD). CMMRD is a condition that usually presents in childhood and causes an increased risk for brain cancer, leukemia, lymphoma and Lynch syndrome associated cancers.

A Summary of Screening Based of of NCCN Guidelines:

Colon and Rectal (Colorectal):  FULL Colonoscopy at age 20-25y or 2-5y prior to the earliest colon cancer if it is diagnosed before age 25y and repeat every 1-2y.
Stomach/Upper GI EGD (to be done at the time of the colonoscopy) depending on center of care. Selected individuals with a family history of gastric, duodenal, or more distal small bowel cancer may have increased risk and may benefit from screening.Individuals of Asian descent may have increased risk for stomach cancer and may benefit from screening.

If screening is done, consider upper endoscopy with visualization of the duodenum and the time of colonoscopy every 3-5 years starting at age 40. Consider H. pylori testing and treatment if detected.

Uterus (Endometrial) Discuss limitations of endometrial cancer surveillance. Know the signs and symptoms like abnormal vaginal bleeding.Risk-reducing hysterectomy and salpingo-oophorectomy (RRSO) are options when childbearing is complete or not desired, ideally by age 40. Follow high-risk RRSO protocol for surgery and pathology.
Ovarian  Discuss limitations of ovarian cancer surveillance. Symptoms of ovarian cancer include persistent (>2 weeks) of abdominal bloating, changes in bowel habits, frequent urination, or early satiety.*The risk of ovarian cancer in women with PMS2 mutations is unclear. Therefore, the benefit of pre-menopausal salpingo-oophorectomy is unclear. Women should discuss the option of salpingo-oophorectomy with their providers on an individual basis.
Bladder and Ureter If there is a family history of bladder and/or ureter cancer, consider surveillance with urine cytology and urinalysis (with micro) every year from age 30, including discussion of benefits and limitations. Routine cystoscopy is not indicated if the results of these tests are normal.
Pancreatic  Dependent on care center. No national guidelines or protocols. Patients can consider clinical trials and research studies for pancreatic cancer screening.
Breast and Prostate Not enough increase in risk to recommend additional screening at this time.
Skin Skin self-exam and report new lesions to doctor.


Aspirin may decrease risk, but optimal dose and duration are uncertain. Talk to gastroenterologist for discussion of personal risks and benefits.

Oral contraceptives lower the risk of ovarian cancer by 50% when taken for 3-5 years and also lower endometrial cancer risk. Depo-medroxyprogesterone acetate (depo Provera) and Levonorgestrol (Mirena) intrauterine system may also be used for endometrial cancer risk reduction.

Avoid Smoking

To learn more about Lynch syndrome please visit our Lynch Syndrome group

Senter, L. et. al. “The Clinical Phenotype of Lynch Syndrome Due to Germ-Line PMS2 Mutations.” Gastroenterology. 2008;135:419-428.