Hereditary Cancer and Genetic Testing

Risk management for people with inherited PMS2 mutations

The National Comprehensive Cancer Network (NCCN) provides risk management guidelines for men and women with PMS2 mutations.  We recommend that you speak with a genetics expert who can look at your personal and family history of cancer and can help you determine the best risk management plan. You can learn more about risk management options in our section on Screening and Risk Reduction by Cancer Type

NCCN risk management guidelines for people with PMS2 mutations include information on the following cancers:


Colorectal Cancer 

  • Colonoscopy beginning between ages 30-35 (or 2-5 years before the earliest age of colon cancer in the family, if diagnosed before age 25).
  • Repeat coloscopy every 1-2 years. You should speak with your doctor about whether your screenings should be yearly or every two years. Men, people over age 40, and people with a personal history of colon cancer or colon polyps may benefit most from yearly screenings. 
  • Daily aspirin can decrease the risk for colorectal cancer. The best dose and timing for aspirin is not known. Recent research found that 600 mg of aspirin taken daily lowered the risk for colorectal cancer in people with Lynch syndrome. Speak with your doctor about the benefits and risks, best timing and dose.


Endometrial cancer 

  • Symptom awareness and biopsy: Endometrial cancer can often be caught early based on symptom awareness followed by a biopsy. For this reason, experts recommend that all women should be aware of endometrial symptoms and immediately report any of the following to their doctor. 
    • unusual vaginal bleeding
    • pelvic or abdominal pain
    • bloating or distended belly
    • difficulty eating
    • increased urination or pressure to urinate 
  • Screening: In the absence of symptoms, regular endometrial cancer screening through transvaginal ultrasound and/or endometrial biopsies does not appear to improve outcomes any better than symptom awareness followed with biopsy for any woman showing symptoms. Despite this, some women undergo regular screening through transvaginal ultrasound and endometrial biopsies. Transvaginal ultrasound is not recommended for premenopausal women. Women should speak with their doctors about the benefits, risks, costs and timing of transvaginal ultrasound and endometrial biopsies in order to make a decision about screening. 
  • Surgery: Removal of the uterus (hysterectomy) lowers the risk for endometrial cancer in women with Lynch syndrome. However, hysterectomy has not been shown to lower the risk for death from endometrial cancer. Women should speak with their doctor about the benefits and risks of hysterectomy after they complete childbearing. The best timing for surgery varies by gene mutation and family history of cancer. 
  • Medication: Oral contraceptive pills (birth control) may lower the risk for endometrial cancer in women with Lynch syndrome. Women should speak with their doctors about the benefits, risks and timing of oral contraceptives. 


Other cancers

NCCN includes the following cancers in their guidelines for risk management in people with PMS2 mutations. However, they note that there is very little evidence of increased risk or benefit from management (unless there is a family history):


Ovarian cancer

  • Surgery: According to experts, there is not enough evidence to recommend removal of the ovaries and fallopian tubes (salpingo-oophorectomy) for all women with a PMS2 mutation. Women should speak with their doctor about the benefits and risks of salpingo-oophorectomy after they complete their childbearing. For women who decide on surgery, the best timing for surgery is unknown.
  • Symptom awareness: Experts recommend that all women should be aware of ovarian cancer symptoms. Women should report to their doctor any of the following symptoms that persist for several weeks and are a change from normal:
    • pelvic or abdominal pain
    • bloating or distended belly
    • difficulty eating
    • feeling full sooner than normal
    • increased urination or pressure to urinate 
  • Screening: In the absence of symptoms, some women undergo regular screening through transvaginal ultrasound and CA125 blood tests. However, ovarian cancer screening does not detect ovarian cancer early. Women should speak with their doctors about the benefits, risks, costs and timing of transvaginal ultrasound and CA125.  
  • Medication: Oral contraceptive pills (birth control) may lower the risk for ovarian cancer in women with Lynch syndrome. Women should speak with their doctors about the benefits, risks and timing of oral contraceptives. 


Pancreatic cancer screening for people with a family history

  • People with a PMS2 mutation who have a first- or second-degree relative with pancreatic cancer, should consider screening beginning at age 50 or 10 years younger than the age of diagnosis of that relative. 
  • For people who choose pancreatic cancer screening, NCCN recommends that the screening be performed in an experienced facility, ideally under research conditions. Before undergoing screening, people should have a conversation with their doctor about the potential benefits, risks, costs and limitations of screening.
  • Consider annual screening with contrast-enhanced MRI/MRCP (magnetic resonance cholangiopancreatography) and/or EUS (endoscopic ultrasound).


Bladder, kidney and ureteral cancer

  • For people from families with a history of urinary tract cancer, consider annual urinalysis beginning between ages 30-35. 


Brain cancer

  • Consider annual physical exam and neurologic exam beginning at age 25 - 30. 


Stomach cancer

  • For people with a family history of stomach cancer and/or people of Asian ancestry:
    • Consider stomach cancer screening using a procedure known as EGD (esophagogastroduodenocopy) every 3-5 years beginning at age 40.
    • If gastric screening is performed, considered testing for and treating H. pylori.


Breast cancer

  • Manage breast cancer risk based on family history. Risk-reducing mastectomy (surgical removal of the breasts) is not typically recommended.
find-support

If you are a person with an PMS2 mutation, you can find peer support through the following resources:

clinical-trials

The following screening and prevention studies are open to people with an inherited PMS2 mutation. 

Multiple cancers

Colorectal cancer

Endometrial cancer

Prostate cancer

Pancreatic cancer

Visit our Research Search and Enroll Tool to find additional prevention and screening studies.