Risk management for people with inherited PMS2 mutations

The National Comprehensive Cancer Network (NCCN) provides risk management guidelines for people 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 
• endometrial cancer
• other cancers

People with an PMS2 mutation may also qualify for clinical trials looking for more effective screening or prevention for cancer.

Colorectal Cancer 

• Begin colonoscopy 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 1-3 years. You should speak with your doctor about the frequency of your screening. 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. 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. Be aware of endometrial cancer symptoms and immediately report any of the following to your 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 anyone showing symptoms. Despite this, some people undergo regular screening through transvaginal ultrasound and endometrial biopsies.
  • Speak with your doctor about the benefits, risks, costs and timing of transvaginal ultrasound and endometrial biopsies in order to make a decision about screening.
  • For those who choose screening, endometrial biopsy every 1-2 years may begin at age 30-35.
  • Annual transvaginal ultrasound to detect endometrial cancer is not recommended for screening until after menopause. 

• Surgery: Removal of the uterus (hysterectomy) lowers the risk for endometrial cancer. However, hysterectomy has not been shown to lower the risk for death from endometrial cancer. Speak with your doctor about the benefits and risks of hysterectomy after you have completed 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 associated with Lynch syndrome. Speak with your doctor 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
• pancreatic cancer
• urinary tract cancer 
• brain cancer
• stomach cancer
• skin cancer

Ovarian cancer

• Surgery: There is not enough evidence to recommend removal of the ovaries and fallopian tubes (salpingo-oophorectomy) for all people with a PMS2 mutation. Speak with your doctor about the benefits and risks of salpingo-oophorectomy after you have completed childbearing. 

• Symptom awareness: Experts recommend that people become aware of ovarian cancer symptoms. Report to any of the following symptoms that persist for several weeks and are a change from normal to your doctor:
  • 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 people undergo regular screening through transvaginal ultrasound and CA125 blood tests. However, ovarian cancer screening does not detect ovarian cancer early. If you are not planning surgery, speak with your doctor 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 people with Lynch syndrome. Speak with your doctor 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. 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

• Learn the signs of brain cancer and report any symptoms to your doctor. 

Stomach cancer

• Begin stomach cancer screening at age 30-40 using a procedure known as EGD (esophagogastroduodenocopy) and repeat every 2-4 years. 
  • Earlier onset screening may be recommended based on family history.
  • More frequent screening may be recommended based on prior screening findings. 
• If gastric screening is performed, considered random biopsy to test for H. pylori. If gastric biopsy is not performed, consider non-invasive testing for H. pylori.
  • People who test positive should receive treatment for H. pylori. 
     

Skin cancer

• Consider skin exam every 1-2 years with an expert trained in finding skin changes related to Lynch syndrome. 
   

Breast cancer

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