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Gene Results

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PMS2 gene

Associated Syndrome Name: Lynch syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

PMS2 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
ColorectalHigh Risk
EndometrialHigh Risk
GastricElevated Risk
OvarianElevated Risk
PancreaticElevated Risk
ProstateElevated Risk
OtherHigh Risk

PMS2 gene Overview

Lynch syndrome 1, 2, 3, 4, 5, 6, 7, 8, 9, 10
  • Individuals with mutations in PMS2 have a condition called Lynch syndrome. This condition is also known as Hereditary Non-Polyposis Colon Cancer (HNPCC).
  • Men and women with Lynch syndrome due to mutations in PMS2 have a high risk of developing colorectal cancer, often at younger ages than seen in the general population. Colorectal cancer in patients with Lynch syndrome develops from adenomatous polyps which progress to cancer more quickly than polyps in individuals who do not have Lynch syndrome.
  • Women with Lynch syndrome due to mutations in PMS2 have a high risk for developing endometrial cancer and possibly an elevated risk for ovarian cancer, often at younger ages than typical in the general population.
  • Patients with Lynch syndrome due to mutations in PMS2 are also believed to have an increased risk of developing a wide variety of other Lynch syndrome associated cancers, including gastric, small bowel, urinary tract, hepatobiliary tract, brain (usually glioblastoma), sebaceous gland, and pancreatic. Precise risk estimates are not available because there is less information available for patients with PMS2 mutations compared with patients who have mutations in other Lynch syndrome genes. These risks may be more significant in patients with a family history of these cancers. Therefore, the general screening and management recommendations provided below should be modified based on individualized risk assessment and counseling.
  • An increased risk for prostate cancer has been documented in multiple studies of men with Lynch syndrome. Estimates range from an approximately 2 to 5-fold increase in risk, but the exact increase has not yet been established for men with mutations in PMS2.
  • Studies have investigated the possibility that patients with Lynch syndrome have an increased risk for other cancers, including breast cancer and adrenocortical carcinoma. However, the data are not conclusive at this time and there are currently no medical management guidelines related to these cancers.
  • Patients with Lynch syndrome have a high risk for developing second primary cancers following an initial diagnosis of colorectal or endometrial cancer. This includes a high risk for endometrial cancer in women following colorectal cancer and vice versa, a high risk for a second primary colorectal cancer in any portions of the colon or rectum remaining after surgical treatment, and a high risk for other Lynch associated cancers, such as those of the upper gastrointestinal tract, urinary tract, and other sites.
  • Although there are high risks for cancer in patients with Lynch syndrome, many of these risks can be greatly reduced with appropriate medical management. Guidelines for the medical management of patients with Lynch syndrome have been developed by the National Comprehensive Cancer Network (NCCN) and other expert groups. These are listed below. It is recommended that patients with a PMS2 mutation and a diagnosis of Lynch syndrome be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with this condition.

PMS2 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
ColorectalTo age 704, 11, 12Up to 20%1.8%
EndometrialTo age 704, 11, 12Up to 15%1.7%
Overall cancer risk (Lynch cancers)Risk for a second Lynch-related cancer after a first cancer diagnosis3, 7Increased riskNA
ProstateTo age 803, 5, 8, 9, 12, 13Elevated risk10.9%
OvarianTo age 702, 4, 8, 11, 12Elevated risk0.7%
GastricTo age 702, 4, 8, 11, 12Elevated risk0.4%
Small BowelTo age 702, 4, 8, 11, 12Elevated risk0.1%
Urinary TractTo age 702, 4, 8, 11, 12, 14Elevated risk0.7%
PancreaticTo age 702, 4, 6, 8, 11, 12, 15Elevated risk0.5%
Central Nervous SystemTo age 702, 4, 8, 11, 12Elevated risk0.4%
Hepatobiliary TractTo age 702, 4, 8, 11, 12Elevated risk0.5%
Sebaceous NeoplasmsTo age 702, 4, 8, 11, 12Elevated risk<1.0%

PMS2 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
ColorectalColonoscopy1, 8, 1620 to 35 years, or 2 to 10 years younger than the earliest diagnosis of colorectal cancer in the familyEvery 1 to 2 years
Colorectal surgical evaluation may be appropriate for some patients8IndividualizedNA
Consider the use of aspirin as a risk-reduction agent1, 8IndividualizedIndividualized
EndometrialPatient education about the importance of quickly seeking attention for endometrial cancer symptoms, such as abnormal bleeding or menstrual cycle irregularities8IndividualizedIndividualized
Consider pelvic examination, endometrial sampling and transvaginal ultrasound.1, 830 to 35 yearsAnnually
Consider hysterectomy.1, 8After completion of childbearingNA
ProstateCurrently there are no specific medical management guidelines for prostate cancer risk in mutation carriers. However, the possibility of an increased risk for prostate cancer can be incorporated into the risk and benefit discussion about offering screening with digital rectal examination (DRE) and Prostate Specific Antigen (PSA).8, 1845 years, or youngerIndividualized
OvarianConsider bilateral salpingo-oophorectomy.1, 8Age 40 or after completion of childbearingNA
Consider transvaginal ultrasound and CA-125 measurement.1, 830 to 35 yearsNA
Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives).8, 20IndividualizedNA
Patient education about ovarian cancer symptoms8IndividualizedNA
GastricConsider testing and treating Helicobacter pylori infection.1IndividualizedNA
Consider upper endoscopy, particularly for patients with additional risk factors for gastric cancer, such as family history or Asian ancestry. Consider biopsy of the antrum.1, 8, 16, 1730 to 40 yearsEvery 2 to 5 years
Small BowelConsider upper endoscopy, particularly for patients with additional risk factors for small bowel cancer, such as family history.1, 8, 1630 to 40 yearsEvery 3 to 5 years
Urinary TractConsider urinalysis.1, 830 to 35 yearsAnnually
PancreaticFor patients with a family history of pancreatic cancer, consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in screening for pancreatic cancer, preferably within research protocols.15, 16Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the familyAnnually
Provide education about ways to reduce pancreatic cancer risk, such as not smoking and losing weight.16, 21IndividualizedIndividualized
Central Nervous SystemPhysical/neurological examination825 to 30 yearsAnnually
Hepatobiliary TractCurrently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers.8NANA
Sebaceous NeoplasmsCurrently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers.NANA
For Patients With A Cancer DiagnosisFor patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., antibodies to PD-1)19NANA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the PMS2 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

In rare instances, an individual may inherit mutations in both copies of the PMS2 gene, leading to the condition Constitutional Mismatch Repair-Deficiency syndrome (CMMR-D). Individuals with CMMR-D often have significant complications in childhood, including colorectal polyposis and a high risk for colorectal, small bowel, brain, and hematologic cancers. Individuals with CMMR-D often have café-au-lait spots. The children of this patient are at risk of inheriting CMMR-D only if the other parent is also a carrier of a PMS2 mutation. Screening the other biological parent of any children for PMS2 mutations may be appropriate.2, 4

Parents who are concerned about the possibility of passing on a PMS2 mutation to a future child may want to discuss options for prenatal testing and assisted reproduction techniques, such as pre-implantation genetic diagnosis (PGD).8


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  2. Kohlmann W, Gruber SB. Lynch Syndrome. 2018 Apr 12. In:Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from PMID: 20301390.
  3. Win AK, et al. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. J Natl Cancer Inst. 2012 104:1363-72. PMID: 22933731.
  4. Senter L, et al. The clinical phenotype of Lynch syndrome due to germline PMS2 mutations. Gastroenterology. 2008 135419-28. PMID: 18602922.
  5. Raymond VM, et al. Elevated risk of prostate cancer among men with Lynch syndrome. J Clin Oncol. 2013 31:1713-8. oi: 10.1200/JCO.2012.44.1238. Epub 2013 Mar 25. PMID: 23530095.
  6. Kastrinos F, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009 302:1790-5. PMID: 19861671.
  7. Win AK, et al. Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst. 2013 105:274-9. PMID: 23385444.
  8. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 3.2019. Dec 13. Available at
  9. Ryan S, et al. Risk of prostate cancer in Lynch syndrome: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014 23:437-49. PMID: 24425144.
  10. Lin KM, et al. Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population. Dis Colon Rectum. 1998 41:428-33. PMID: 9559626.
  11. ten Broeke SW, et al. Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk. J Clin Oncol. 2015 33:319-25. PMID: 25512458.
  12. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. (Accessed on 1-2-2017)
  13. Grindedal EM, et al. Germ-line mutations in mismatch repair genes associated with prostate cancer. Cancer Epidemiol Biomarkers Prev. 2009 18:2460-7. PMID: 19723918.
  14. Møller P, et al. Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut. 2017 [Epub ahead of print] PMID: 28754778.
  15. Goggins M, et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020 69:7-17. PMID: 31672839.
  16. Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
  17. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 4.2019. Dec 20. Available at
  18. Carroll PR, et al. NCCN Clinical Practice Guidelines in Oncology®: Prostate Cancer Early Detection. V 2.2019. May 31. Available at
  20. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic. V 1.2020. Dec 4. Available at
  21. Tempero MA, et al. NCCN Clinical Practice Guidelines in Oncology®: Pancreatic Adenocarcinoma. V 1.2020. Nov 26. Available at
Last Updated on 11-Nov-2021