Cancer risk associated with inherited mutations in Lynch syndrome genes
Full article: https://www.nature.com/articles/s41436-019-0596-9
Lynch syndrome is the most common inherited cause of cancer affecting about 1 in 300 people. People with Lynch syndrome have an increased risk of colorectal endometrial and other cancers. A large study followed people with mutations in the Lynch syndrome genes MLH1, MSH2, MSH6 and PMS2 to determine the risk of other types of cancer. (2/21/20)
Guidelines for risk management of Lynch syndrome
The National Comprehensive Cancer Network (NCCN) has guidelines for cancer risk management in people with a Lynch syndrome mutation.
Guidelines for men and women
- Colonoscopy every 1-2 years beginning at age 20-25 (or 2-5 years prior to the earliest colon cancer in the family).
- Experts suggest daily aspirin to decrease the risk for colorectal cancer in people with Lynch syndrome, but the best dose is not known.
- Consider gastric cancer screening every 3-5 years beginning at age 40 if there is a family history of gastric cancer and/or Asian ancestry. If gastric screening is performed, considered testing for and treating H. pylori.
- Consider annual urinalysis beginning age 30-35, especially for people from families with a family history of urothelial cancer and men with an MSH2 mutation.
- Consider annual physical and neurological exam starting at age 25-30.
- For patients of reproductive age, be advised about options for prenatal diagnosis and assisted reproduction including pre-implantation genetic diagnosis.
Additional guidelines for women
- Consider risk-reducing removal of ovaries and uterus upon completion of childbearing.
- Women should be educated on possible symptoms of ovarian or uterine cancer. Report any unusual vaginal bleeding, pelvic or abdominal pain, bloating, increased abdominal girth, difficulty eating, or increased urinary frequency or urgency to health care providers immediately.
- Consider screening via endometrial biopsy every 1-2 years.
- Manage breast cancer risk based on family history.
- Experts do not currently recommend pancreatic cancer screening for people with a mutation associated with Lynch Syndrome who do not have a close family history of pancreatic cancer
- People with a mutation in MLH1, MSH2, MSH6 and EPCAM and those with a family history of pancreatic cancer, are encouraged to discuss the pros and cons of annual screening for pancreatic cancer their health care provider. The International Cancer of the Pancreas Screening (CAPS) consortium recommends that patients with LS with one first-degree relative with pancreatic cancer should be considered for screening.
- For those who decide to undergo pancreatic cancer screening, consider beginning at age 50 or 10 years earlier than the earliest pancreatic cancer diagnosis in the family.
- Screening be ideally performed at a center with expertise.
- People with a Lynch Syndrome gene mutation may also be eligible for pancreatic cancer screening clinical trials. Visit our research study page for links to clinical trials for early detection of pancreatic cancer.
Risk to relatives
- Patients should be advised about possible inherited cancer risk to relatives, options for risk assessment, and management.
- Genetic counseling and consideration of genetic testing is recommended for at risk-relatives.
Questions To Ask Your Health Care Provider
- I have a mutation in a Lynch syndrome gene, what cancer screening tests do you recommend?
- My family has a history of colorectal, pancreatic, stomach, ovarian or other cancers, should I consider genetic testing?
- What are the preventive options for reducing my cancer risk?
- What are the signs or symptoms of cancers that I am most at risk for and when should I seek evaluation from my healthcare provider?
- I have Lynch syndrome and I’ve been diagnosed with cancer. Does my Lynch syndrome mutation affect my treatment options?
Open Clinical Trials
The following studies are enrolling people with a mutation linked to Lynch syndrome:
- 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, in order to study gynecologic cancer risks. All patients will be enrolled at MD Anderson.
- NCT04125914: Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families. This trial studies how well weight management and health behavior intervention works in helping patients with hereditary breast and ovarian cancer and Lynch syndrome mutation carriers lose or maintain a healthy weight and lower their risk for cancer
- NCT00927680: Familial Colorectal Cancer Registry in Hispanics (PURIFICAR). This study will serve as the foundation for our large, island-wide, population-based, genetic-epidemiologic study of familial colorectal cancer in Puerto Rico.
- NCT00582296: Multi-Organ Screening Recommendations in Patients With Lynch Syndrome. The purpose of this study is to examine how people with a family history of colon cancer and other related cancers respond to recommendations for cancer screening after genetic counseling.
- NCT03805919: Men at High Genetic Risk for Prostate Cancer. The goal of this research is to study men with specific genetic changes and determine who is at higher risk for getting prostate cancer. Men ages 30-75 who have a mutation in one of the following genes will be eligible: BRCA 1 and 2, DNA Mismatch Repair (MMR) genes associated with Lynch syndrome, (MLH1, MSH2, MSH6, PMS2, and EPCAM), HOXB13, ATM, NBN, TP53 CHEK2, PALB2, RAD51D, or FANCA.
- NCT02206360: Pancreatic Cancer Early Detection Program (PCEDP). This study uses ultrasound or MRI to test early detection of pancreatic cancer. Early detection testing is recommended for individuals at elevated risk for the development of Pancreatic Cancer. Known carrier of any of the following mutations (BRCA1, MLH1, MSH2, PMS2, MSH6, EPCAM , P53, PALB2, APC, or ATM) PLUS first or second degree relative affected with pancreatic cancer;
- NCT02775461: Pancreas Registry and High Risk Registry. The purpose of this study is to establish a registry of patients with pancreatic diseases. Patients included in the registry may include those with: pancreatic cancer, precancerous lesions of the pancreas, inflammatory lesions of the pancreas, cystic lesions of the pancreas, and patients at high-risk of pancreatic cancer such as those with a family history of pancreatic cancer or with a family history of a syndrome known to be associated with pancreatic cancer.
- NCT03762590 GENetic Education Risk Assessment and TEsting Study (GENERATE). The goal of the GENERATE study is to improve genetic testing and cancer prevention in family members of pancreatic cancer patients with identified genetic mutations (inherited changes). Eligible participants are people who themselves have not had genetic counseling and have a close relative with pancreatic cancer or a relative with a mutation in one of the following genes: APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53.
FORCE is a national nonprofit organization, established in 1999. Our mission is to improve the lives of individuals and families affected by adult hereditary cancers.