Lynch syndrome, also called hereditary nonpolyposis colorectal cancer (HNPCC), is a dominantly inherited cancer syndrome which confers a predisposition to colorectal, endometrial, and other cancers. As a dominantly inherited cancer syndrome, 50% of a patient’s offspring and/or siblings may inherit it.6
The underlying defect in Lynch syndrome is in the cellular mismatch repair system, which detects and corrects DNA replication errors. Lynch syndrome confers substantially elevated risks for specific cancers, earlier onset of disease, high rates of multiple primary cancers, and the absence of typical risk factors (Table 1).7
Here we present a case in which a female patient and her sister were both diagnosed with Lynch syndrome in their 30s, illustrating the complex care and surveillance provided by the Cancer Risk Management Program.
The case patient was diagnosed with endometrial cancer at age 32. Her sister was diagnosed with endometrial cancer at age 33. Due to this unusual family history, the case patient was referred to us for genetic counseling.
The genetic counselor obtained a pedigree (Table 2) which revealed, in addition to these two endometrial cancers, a grandmother who was diagnosed with both stomach and colon cancers in her 30s. Lynch syndrome was the primary potential diagnosis based on the family history. Genetic testing for Lynch syndrome was ordered. The case patient was found to have an MSH2 mutation known to be associated with Lynch syndrome. The patient’s sister was also subsequently tested and was found to have the same genetic mutation.
Both sisters came to our program to coordinate their surveillance plan for cancer and were given complete education about the risks associated with Lynch syndrome. The case patient’s sister decided to have a prophylactic bilateral oophorectomy. Upon removal of her ovaries, it was discovered that she had a Grade 1 mucinous cystadenocarcinoma of the right ovary. Both sisters continue to have their care coordinated through the program and undergo regular screenings.
Surveillance recommendations for Lynch syndrome differ substantially from the general population. Surveillance for colon cancer should include annual or biannual colonoscopy beginning around age 25.8 Prophylactic removal of the uterus and ovaries once childbearing is complete is recommended, due to the lack of effective surveillance of the ovaries and the significant decrease in the risk for both cancers following surgery.9 The evidence for other screening protocols is less clear and is determined on a patient-to-patient basis.
6. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348(10):919-32.
7. Hampel H, Frankel WL, Martin E, et al. Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol. 2008;26(35):5783-8.
8. Vasen HF, Blanco I, Aktan-Collan K, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut. 2013; 62(6):812-23.
9. Schmeler KM, Lynch HT, Chen LM, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006; 354(3):261-9.
10. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/Familial High Risk Assessment: Colorectal, v.2.2014.
Our Cancer Risk Management Program helps patients evaluate their risk of developing cancer and to work with them and their referring healthcare providers to manage cancer risk over the long term.Continue reading