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Lynch Syndrome

7/1/2017 - Janeen Arbuckle M.D., PhD

Mentor: Todd Jenkins MD

Editor: Elizabeth Ferries-Rowe


Lynch syndrome is an autosomal dominant hereditary cancer syndrome which commonly presents with colon cancer, endometrial cancer, or ovarian cancer.  It is also associated with cancers of the stomach, small bowel, hepatobiliary system, renal pelvis, and ureter.  Lynch syndrome is characterized by defects in genes involved in DNA mismatch repair such as MLH1, MSH2, MSH6, and PMS2, mutation of which results in microsatellite instability. Although Lynch syndrome is only responsible for approximately 2% of all colon and endometrial cancers, individuals with Lynch syndrome are at increased risk for the development of these cancers over their lifetime. The risk of cancer depends on the specific inherited gene mutation, with the risk of developing endometrial cancer ranging from 16-61% and the risk of developing colon cancer ranging from 18-61% by age 70.  Women with Lynch syndrome also have an increased risk of ovarian cancer by age 70 relative to the general population (5-10% vs 1.4%). 

Women who are diagnosed with a Lynch syndrome-associated cancer should be screened.  This includes women who have:

  • Uterine or colorectal cancer prior to age 50
  • Two or more synchronous or sequential Lynch syndrome associated malignancies
  • Colorectal cancer with worrisome histologic features (e.g. tumor-infiltrating lymphocytes, signet-ring differentiation, etc.)

In addition, women with a personal history of uterine or colorectal cancer and a family history of a Lynch syndrome-associated malignancy may also warrant screening for Lynch syndrome.  Testing for Lynch syndrome can be done by germline DNA testing of the patient or by testing of the tumor for the expression of mismatch repair genes or for microsatellite instability.

Women with a family history of Lynch syndrome-associated cancers should also be screened.  Women who are at especially high risk are those with a first degree relative with a Lynch syndrome-associated cancer diagnosed prior to age 60. In addition, women with a known family history of Lynch syndrome should be offered referral to a genetic counselor regardless of degree of relation. Germline testing for Lynch syndrome-associated mutations may then be considered.

Women with confirmed Lynch syndrome should be offered surveillance for Lynch syndrome-associated malignancies and should be counseled on options for risk reduction.  Screening for colon cancer in women with Lynch syndrome includes colonoscopy every 1-2 years, starting between the ages of 20-25 or 2-5 years prior to the earliest cancer diagnosis in the family, whichever is earlier.  Screening for endometrial cancer should be done by endometrial biopsy every 1-2 years, starting between the ages of 30-35. Women should keep a menstrual calendar and have additional evaluation in the setting of abnormal bleeding.  No reliable screening testing has been validated for the early detection of ovarian cancer.  Risk reduction may be achieved in reproductive age women through the use of progesterone agents or combined oral contraceptives.  Risk reducing hysterectomy with bilateral salpingo-oophorectomy should be considered in women in their early to mid-40s or upon the completion of childbearing.


Further reading:

Lynch syndrome. Practice Bulletin No. 147. American College of Obstetricians and Gynecologists. Obstet Gynecol 2014;124:1042–54, doi: 10.1097/01.AOG.0000456325.50739.72

Giardiello, FM, et al. Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2014; 109:1159–79, DOI: 10.1097/DCR.000000000000000

Provenzale D, et al. Genetic/Familial High-Risk Assessment: Colorectal Version 1.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2016 Aug;14(8):1010-30., 

 Initial approval July 2017.


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