Mutations in Lynch syndrome genes MSH6 and PMS2 may be associated with breast cancer

Expert Guidelines

The National Comprehensive Cancer Network (NCCN) provides risk management guidelines for people with Lynch syndrome mutations.

Colorectal cancer 

• Colonoscopy every 1-2 years. Speak with your doctor about whether you should be screened yearly or every two years. Men, people over age 40 and individuals with a personal history of colon cancer or colon polyps may benefit most from yearly screenings. 
  • For people with MLH1, MSH2 or EPCAM:
    • beginning between ages 20-25 (or 2-5 years before the earliest age of colon cancer in the family, if diagnosed before age 25).
  • For people with MSH6 or PMS2: 
    • beginning between ages 30-35 (or 2-5 years before the earliest age of colon cancer in the family, if diagnosed before age 35).
• Daily aspirin can decrease the risk of colorectal cancer. The best dose and timing for aspirin are unknown. Speak with your doctor about the benefits, risks, best timing and dose.

Endometrial and ovarian cancer

• Be aware of endometrial and ovarian cancer symptoms.
• Consider endometrial biopsy every 1-2 years beginning between ages 30-35.
• Discuss the benefits and risks of oral contraceptives.
• Consider risk-reducing hysterectomy; discuss risk-reducing removal of ovaries and fallopian tubes with your doctor (EPCAM, MLH1, MSH2 and MSH6 gene mutations).

Other cancers

• Consider annual prostate cancer screening with PSA testing and digital rectal exam.
• For people with a family history of urothelial cancer and men with an MSH2 mutation:
  • Consider annual urinalysis beginning between ages 30-35.
• Consider baseline esophagogastroduodenoscopy with random stomach biopsy at age 40. 
  • consider continuing this surveillance every 3-5 years for people in a high-risk category for gastric cancer. 
• Consider testing for H. pylori and treating if the test is positive. 
• For people with a family history of pancreatic cancer:
  • Consider annual cholangiopancreatography (MRCP) and/or endoscopic ultrasound (EUS) beginning at age 50. 
  • Consider participating in a pancreatic cancer screening study. 

Consider annual physical and neurological exams. 

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Questions To Ask Your Health Care Provider

• Should I consider genetic counseling or genetic testing for Lynch syndrome mutations given my personal and family history?
• My family has a history of Lynch syndrome, should I consider genetic counseling and testing?
• As a Lynch syndrome mutation carrier, what breast cancer screening options should I consider? What are my risks for other cancers?
• As a Lynch syndrome mutation carrier, what preventive measures should I consider?
• Can you refer me to a genetics expert?

Open Clinical Trials

The following screening and prevention studies are open to people with Lynch syndrome. 

Colorectal cancer

• NCT03831698: Omega 3 Fatty Acids in Colorectal Cancer (CRC) Prevention in Patients With Lynch Syndrome (COLYNE). This study is looking at the effects of omega-3 acid ethyl esters capsules (generic Lovaza) on molecular and intestinal microbiota changes in participants at high risk for colorectal cancer.
• NCT04379999: Atorvastatin ± Aspirin in Lynch Syndrome Syndrome. This study will investigate whether a common cholesterol lowering agent (atorvastatin) alone or combined with a nonsteroidal anti-inflammatory drug (aspirin) reduces the risk of colorectal cancer (CRC) in high-risk individuals with Lynch syndrome.

Gynecologic cancers

• NCT05257057: Frequency of Endometrial Cancer Precursors Associated With Lynch Syndrome. The purpose of this study is to examine endometrial hyperplasia specimens and compare the frequency of Lynch syndrome gene mutations between people with endometrial hyperplasia and those with endometrial cancer. 
• NCT00508573: Registry for Women Who Are At Risk Or May Have Lynch Syndrome. The goal of this study is to create a registry of information about women who have or are at risk for Lynch syndrome, to facilitate study of gynecologic cancer risks.
• Validating a Blood Test for Early Ovarian Cancer Detection in High-risk Women and Families: MicroRNA Detection Study (MiDE). The goal of MiDe is to develop a clinical diagnostic test to detect early-onset ovarian cancer, as currently, no reliable screening or early-detection tests are available. Participants can be expected to provide up to 4 tubes of blood every 6 months for up to 5 years. Samples can be collected through mobile phlebotomy all around the US.

Prostate cancer

• NCT03805919: Men at High Genetic Risk for Prostate Cancer. This is a prostate cancer screening study using MRI in high-risk men. This study is open to men with Lynch syndrome and other mutations.
• NCT05129605: Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS).  This study will look at how well prostate MRI works as a screening tool for men at high risk for prostate cancer. This study is open to men with an inherited mutation in ATM, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51C, RAD51D, TP53 and other genes. 

Pancreatic cancer

• NCT02206360: Pancreatic Cancer Early Detection Program. This pancreatic cancer screening study uses esophageal ultrasound to screen for pancreatic cancer in high-risk people. The study is open to people who have a family history of pancreatic cancer and an MLH1 mutation or other mutation linked to increased cancer risk.
• NCT03568630: Blood Markers of Early Pancreas Cancer.  This pancreatic cancer study involves blood samples taken over time to look for biomarkers of pancreatic cancer in high-risk people. The study is open to people with an MLH1 mutation or other mutation linked to increased cancer risk.
• NCT03250078: A Pancreatic Cancer Screening Study in Hereditary High-Risk Individuals. The main goal of this study is to screen and detect pancreatic cancer and precursor lesions in individuals with a strong family history or genetic predisposition to pancreatic cancer. MRI and magnetic cholangiopancreatography (MRI/MRCP) will be utilized to screen for early-stage pancreatic lesions.

Other clinical trials for patients with endometrial cancer can be found here.