Lynch syndrome, now referred to as hereditary nonpolyposis colorectal cancer (HNPCC), was first identified in a family in 1895. In 1966, Henry Lynch reported a series of families with colon and other cancers in the Nebraska area. Today, the evidence shows that HNPCC is associated with germline pathogenic variants in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes.
HNPCC increases patients’ risk for developing a variety of cancers. An estimated 4,000 colorectal and 1,800 endometrial cancers per year are attributed to HNPCC. Those and other cancers may develop in an individual or families, depending on the specific pathogenic variant and individual prevention efforts, including regular colonoscopy and risk-reducing surgery.
People with a known pathogenic variant associated with HNPCC need lifelong screening. Testing is typically offered around age 20–25, the timeframe when intensive screening would begin in a person with HNPCC.
Recommendations for Care
- Colonoscopy with removal of polyps every one to two years beginning at age 20–25 or five years before the youngest diagnosis of colorectal cancer in the family (whichever is earliest)
- Upper endoscopy every three to five years beginning at age 30–35. Biopsies should be evaluated for H. pylori infections and appropriate treatment administered as indicated.
- Annual urine analysis beginning at age 30–35
- Annual physical exam, including neurologic evaluation, beginning at 25–30
- Annual mammogram and breast magnetic resonance imaging alternating every six months beginning at age 30 with a clinical breast examination. Educate patients about breast self-awareness and the importance of prompt evaluation of any breast changes.
- Transvaginal ultrasound screening of the ovaries every six months beginning at age 30 until the patient is ready to consider surgical options. Surgery to remove the ovaries, fallopian tubes, and uterus is recommended at age 35–45, once childbearing is complete.
- Annual full body skin examination for sebaceous adenoma and melanoma. Instruct patients on changes associated with melanoma that should be promptly evaluated. Educate them about decreasing ultraviolet exposure, consistently using sunscreen with an SPF of 30, and wearing protective clothing, including hats and sunglasses.
- Consider pancreatic cancer screening at age 40 or 10 years before the youngest pancreatic cancer in the family with magnetic resonance cholangiopancreatography or endoscopic ultrasound, fasting blood glucose, and HbA1c.
- Annual prostate screening beginning at age 45 or earlier depending on family history, including digital rectal examination and prostate-specific antigen testing
Patients and families with HNPCC need ongoing support and education to ensure that the extensive screening guidelines are followed. As children in these families approach the age of 20–25, they should be offered the option of testing to clarify risk and whether they would benefit from more intensive screening. Supportive educational messages should reiterate that early detection of cancers is possible with appropriate screening and that risk-reducing measures will help in cancer prevention, ultimately decreasing the morbidity and mortality associated with an HNPCC diagnosis.