Genetic Evaluation and Management of Lynch Syndrome

Publication Date: August 1, 2014
Last Updated: March 14, 2022



Testing for MMR deficiency of newly diagnosed CRC should be performed. This can be done for all CRCs, or CRC diagnosed at age 70 years or younger, and in individuals older than 70 years who have a family history concerning for LS. Analysis can be done by IHC testing for the MLH1 / MSH2 / MSH6 / PMS2 proteins and / or testing for MSI. Tumors that demonstrate loss of MLH1 should undergo BRAF testing or analysis of MLH1 promoter hypermethylation. To facilitate surgical planning, tumor testing on suspected CRC should be performed on preoperative biopsy specimens, if possible. (III, B)
Individuals who have a personal history of a tumor showing evidence of MMR deficiency (without evidence of MLH1 promoter methylation); uterine cancer diagnosed at younger than age 50 years; a known family MMR gene mutation; fulfill Amsterdam criteria or revised Bethesda guidelines; and / or have a personal risk of ≥5 % chance of LS based on prediction models should undergo genetic evaluation for LS. (III, B)
(strong recommendation)


Screening for CRC by colonoscopy is recommended in persons at risk (first-degree relatives of those affected) or affected with LS every 1 to 2 years, beginning between ages 20 – 25 years or 2 – 5 years before the youngest age of diagnosis of CRC in the family if diagnosed before age 25 years. In surveillance of MMR germline mutation-positive patients, consideration should be given to annual colonoscopy. (III, B)
In carriers of deleterious MSH6 and PMS2 mutations, the risk of CRC is lower and age at diagnosis later than in patients with MLH1 and MSH2 mutations. In these affected individuals, consideration could be given to starting screening at age 30 years in MSH6 and 35 years in PMS2 carriers, unless an early-onset cancer exists in a given family.
(strong recommendation)
The age of onset and frequency of colonoscopy in this guideline is in agreement with most organizations and authorities.
Screening for EC should be offered to women at risk for or affected with LS by pelvic examination and endometrial sampling annually starting at age 30 – 35 years. (V, C)
( expert consensus in concert with other expert opinion)
Screening for ovarian cancer should be offered to women at risk for or affected with LS by transvaginal ultrasound annually starting at age 30 – 35 years. (V, C)

In the absence of data on this issue, several consensus panels have suggested that transvaginal ultrasound for ovarian cancer is a screening consideration in LS.

(expert consensus)
Hysterectomy and bilateral salpingo-oophorectomy should be recommended to women with LS who have finished childbearing or at age 40 years. Patient considerations in this decision could include differences in uterine cancer risk, depending on MMR gene mutation; morbidity of surgery; and the risk of menopausal symptoms, osteoporosis, and cardiac disease if hormone replacement therapy is not given. (IV, B)
(observational study)
This recommendation is in agreement with the Mallorca Group. The NCCN recommends considering prophylactic surgery after child bearing is completed.
Screening for gastric cancer should be considered in persons at risk for or affected with LS by esophagogastroduodenoscopy (EGD) with gastric biopsy of the antrum at age 30 – 35 years with treatment of H. pylori infection when found. Subsequent, surveillance every 2 – 3 years can be considered based on individual patient risk factors. (V, C)
(expert consensus)

This guideline is in concert with that of the NCCN. The Mallorca group recommends initial screening EGD with biopsy without a recommendation for ongoing surveillance

Routine screening of the small intestine is not recommended. (, )
This guideline is in concert with the Mallorca group, which does not recommend routine screening of the small intestine, but suggests attention to investigation of the distal duodenum and ileum during endoscopic studies. The NCCN suggests capsule endoscopy screening can be considered at 2 – 3 year intervals beginning at age 30– 35 years.
Screening for cancer of the urinary tract should be considered for persons at risk for or affected with LS, with urinalysis annually starting at age 30 – 35 years. (V, C)
(expert consensus)
The guideline is in concert with the NCCN. The Mallorca group does not recommend routine screening for urinary cancers.
Routine screening of the pancreas is not recommended. The benefit of screening for pancreatic cancer with this magnitude of risk is not established. (, )

This recommendation is in concert with other societies. However, an international pancreas consensus panel recommends that MMR gene mutation carriers with 1 affected first degree relative with pancreatic cancer should be considered for screening.

Routine screening of the prostate and breast cancer is not recommended beyond what is advised for the general population.

This recommendation is in concert with other societies.

Colectomy with ileorectal anastomosis is the primary treatment of patients affected with LS with colon cancer or colon neoplasia not removable by endoscopy. Consideration for less extensive surgery should be given in patients older than 60 – 65 years of age and those with underlying sphincter dysfunction. (III, B)
(strong recommendation)

The NCCN and Mallorca group both recommend colectomy with ileorectal anastomosis with no deference to patient age.

Growing but not conclusive evidence exists that use of aspirin is beneficial in preventing cancer in LS patients. Treatment of an individual patient with aspirin is a consideration after discussion of patient-specific risks, benefits, and uncertainties of treatment is conducted. (I, B)

This approach is endorsed by the Mallorca group and the NCCN.


Recommendation Grading




Genetic Evaluation and Management of Lynch Syndrome

Authoring Organizations

Publication Month/Year

August 1, 2014

Last Updated Month/Year

June 27, 2023

Document Type


External Publication Status


Country of Publication


Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings


Intended Users

Nurse, nurse practitioner, physician, physician assistant


Assessment and screening, Diagnosis, Management

Diseases/Conditions (MeSH)

D055847 - Lynch Syndrome II


genetic testing, colorectal cancer, Lynch syndrome

Supplemental Methodology Resources

Methodology Supplement