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
OtherElevated Risk
OvarianElevated Risk
PancreaticElevated Risk
ProstateElevated Risk
SkinElevated Risk

PMS2 gene Overview

Lynch syndrome 1, 2, 3, 4, 5, 6, 7, 8, 9
  • Individuals with mutations in PMS2 have Lynch syndrome. This condition is also known as Hereditary Non-Polyposis Colorectal 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.
  • There is still some uncertainty as to whether patients with Lynch syndrome due to PMS2 mutations have significantly increased risks for the wide variety of cancers associated with Lynch syndrome due to mutations in other genes. These cancers include small bowel, urinary tract, hepatobiliary tract, brain (usually glioblastoma), sebaceous gland, prostate, and pancreatic. In some cases, 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. However, it is clear that the risks associated with PMS2 mutations are not nearly as high as the risks seen with other Lynch syndrome genes.
  • Cancer risks may be more significant in patients with a family history of particular cancers. Therefore, the general screening and management recommendations provided below should be modified based on individualized risk assessment and counseling.
  • Patients with Lynch syndrome due to mutations in PMS2 may have an increased risk for gastric cancer. Screening may be particularly important for patients with additional risk factors for gastric cancer, such as being male, older age, first-degree relative with gastric cancer, Asian ethnicity, residing in, or immigrating from countries with high background incidence of gastric cancer, chronic autoimmune gastritis, gastric intestinal metaplasia, and gastric adenomas.
  • 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 702, 3, 10, 11, 12Up to 20%1.8%
EndometrialTo age 701, 2, 3, 10, 12, 13, 1412%-26%1.9%
Overall cancer risk (Lynch cancers)Risk for a second Lynch-related cancer after a first cancer diagnosis15, 16Increased riskNA
ProstateTo age 702, 3, 12, 13Possibly elevated risk6.1%
OvarianTo age 702, 3, 12, 13Possibly elevated risk0.6%
GastricTo age 703, 12Possibly elevated risk0.3%
Small BowelTo age 703, 12, 13, 14Possibly elevated risk0.1%
UrothelialTo age 702, 3, 12Possibly elevated risk0.7%
PancreaticTo age 7012, 14Possibly elevated risk0.6%
BrainTo age 702, 3, 12, 13Possibly elevated risk0.4%
Hepatobiliary TractTo age 703, 12, 14Possibly elevated risk0.5%
Lynch-associated Skin TumorsTo age 707, 10, 17, 18Elevated 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)
ColorectalColonoscopy1830 to 35 years, or 2 to 5 years younger than the earliest colorectal cancer diagnosis in the family if it is under age 30Every 1 to 2 years
Consider the use of aspirin as a risk-reduction agent18IndividualizedIndividualized
EndometrialPatient education about the importance of quickly seeking attention for endometrial cancer symptoms, such as abnormal bleeding or menstrual cycle irregularities18IndividualizedIndividualized
Consider pelvic examination, endometrial sampling and transvaginal ultrasound.1830 to 35 yearsEvery 1 to 2 years
Consider hysterectomy.18After completion of childbearingNA
ProstateIncorporating information about increased risk due to gene mutation, start risk and benefit discussion about offering baseline digital rectal examination (DRE) and Prostate Specific Antigen (PSA).18, 20Age 40Individualized, consider annually
OvarianConsider bilateral salpingo-oophorectomy.18After completion of childbearingNA
Consider transvaginal ultrasound and CA-125 measurement.1830 to 35 yearsNA
Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives).18, 22IndividualizedNA
Patient education about ovarian cancer symptoms18IndividualizedNA
GastricConsider testing and treating Helicobacter pylori infection.18IndividualizedNA
Consider upper endoscopy, particularly for patients with additional risk factors (see clinical overview). Consider biopsy of the proximal and distal stomach.18, 1940 yearsEvery 3 to 5 years
Small BowelConsider upper endoscopy, particularly for patients with additional risk factors for small bowel cancer, such as family history.1830 to 40 yearsEvery 3 to 5 years
UrothelialConsider urinalysis.1830 to 35 yearsAnnually
PancreaticCurrently there are no specific medical management guidelines for the possibly increased risk for pancreatic cancer in mutation carriers.NANA
BrainPatient education about the importance of quickly seeking attention for signs and symptoms of neurologic cancer18IndividualizedNA
Hepatobiliary TractCurrently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers.18NANA
Lynch-associated Skin TumorsConsider skin exams18IndividualizedEvery 1 to 2 years
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)21NANA

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.

This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males who have this/these mutation(s) are provided below.

Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers and sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance of carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention.

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.7, 10

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).18


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Last Updated on 29-Sep-2022