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MSH2 gene
Associated Syndrome Name: Lynch syndrome/Hereditary NonPolyposis Colorectal Cancer (HNPCC)
MSH2 Summary Cancer Risk Table
CANCER
Colorectal
GENETIC CANCER
RISK
High Risk
Endometrial High Risk
Gastric
High Risk
Ovarian
High Risk
Pancreatic
Elevated Risk
Other
High Risk
MSH2 gene Overview
Lynch syndrome
1, 2, 3, 4, 5, 6, 7, 8
Individuals with mutations in MSH2 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 MSH2 have a high risk of developing colorectal
cancer, often at young ages. 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 MSH2 have a high risk for developing endometrial and
ovarian cancer, often at young ages.
Patients with Lynch syndrome due to mutations in MSH2 also have an increased risk of developing a wide
variety of other cancers, including gastric, small bowel, urinary tract, hepatobiliary tract, brain (usually
glioblastoma), sebaceous gland, and pancreatic.
Studies have investigated the possibility that patients with Lynch syndrome have an increased risk for
other cancers, including breast cancer, prostate 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
1
(NCCN) and other expert groups. These are listed below. It is recommended that patients with an MSH2
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.
MSH2 gene Cancer Risk Table
CANCER TYPE
AGE RANGE
1, 6
Colorectal
To age 70
Endometrial
To age 70
Overall cancer risk (Lynch
cancers)
Risk for a second Lynchrelated cancer after a first
10, 11
cancer diagnosis
Ovarian
To age 70
Gastric
To age 70
Small Bowel
To age 70
Urinary Tract
To age 70
Pancreatic
To age 70
Hepatobiliary Tract
To age 70
Central Nervous System
To age 70
Sebaceous Neoplasms
To age 70
1, 6
1, 6
1, 6
1, 6
1, 6, 8
1, 2, 6
1, 6
1, 6
1, 6
CANCER RISK
RISK FOR GENERAL
9
POPULATION
52%-82%
1.9%
25%-60%
1.6%
Increased risk
NA
4%-12%
0.7%
6%-13%
0.3%
3%-6%
0.1%
1%-7%, or higher
<1.0%
1%-6%
0.5%
1.4%-4%
0.4%
1%-3%
0.4%
1%-9%
<1.0%
MSH2 Cancer Risk Management Table
The overview of medical management options provided is a summary of professional society guidelines as of the last
Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for
more details 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
Colorectal
2
PROCEDURE
6, 7
Colonoscopy
AGE TO BEGIN
20 to 25 years, or 2
to 5 years younger
than the earliest
diagnosis in family
if it is under age 25
FREQUENCY
Every 1 to 2
years
CANCER TYPE
PROCEDURE
AGE TO BEGIN
Colorectal surgical evaluation may be appropriate for
6
some patients
Individualized
NA
Individualized
Individualized
Patient education about endometrial cancer symptoms.
Individualized
NA
Consider pelvic examination, endometrial sampling and
6, 7
transvaginal ultrasound.
30 to 35 years
Annually
After completion of
childbearing
NA
Consider bilateral salpingo-oophorectomy.
Age 40 or after
completion of
childbearing
NA
Consider transvaginal ultrasound and CA-125
6, 7
measurement.
30 to 35 years
NA
Treat for Helicobacter pylori infection if present.
Individualized
NA
Consider upper endoscopy, particularly for patients
with additional risk factors for gastric cancer, such as
family history or Asian ancestry. Consider biopsy of the
6, 7, 12
antrum.
30 to 35 years
Every 2 to 5
years
Small Bowel
Consider upper endoscopy, particularly for patients
with additional risk factors for small bowel cancer, such
6, 7
as family history.
30 to 35 years
Every 3 to 5
years
Urinary Tract
Consider urinalysis.
30 to 35 years
Annually
Pancreatic
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 the screening for pancreatic cancer,
13
preferably within research protocols.
Individualized
NA
Hepatobiliary
Tract
Currently there are no specific medical management
guidelines for hepatobiliary cancer risk in mutation
6
carriers.
NA
NA
Central
Nervous
System
Physical/neurological examination
25 to 30 years
Annually
6, 7
Consider the use of aspirin as a risk-reduction agent
Endometrial
6
6, 7
Consider hysterectomy.
Ovarian
Gastric
3
FREQUENCY
6, 7
7
6, 7
6
CANCER TYPE
Sebaceous
Neoplasms
PROCEDURE
Currently there are no specific medical management
guidelines for sebaceous neoplasm risk in mutation
carriers.
AGE TO BEGIN
NA
FREQUENCY
NA
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 MSH2 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 MSH2 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 MSH2 mutation. Screening the spouse/partner of this
1
patient for MSH2 mutations may be appropriate.
References
1. Kohlmann W, Gruber SB. Lynch Syndrome. 2014 May 22. In:Pagon RA, et al., editors. GeneReviews®
[Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from
http://www.ncbi.nlm.nih.gov/books/NBK1211/ PMID: 20301390.
2. Kastrinos F, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009 302:1790-5. PMID:
19861671.
3. 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.
4. 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.
5. 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.
6. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment:
Colorectal. V 2.2016. September 26. Available at http://www.nccn.org.
7. 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.
PMID: 25070057.
8. Joost P, et al. Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations. Urology.
2015 86:1212-7. PMID: 26385421.
4
9. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V
8.0.1, Nov 19, 2012.
10. Larsen Haidle J, Howe JR. Juvenile Polyposis Syndrome. 2015 Dec 3. In: Pagon RA, et al., editors.
GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1469/ PMID: 20301642.
11. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Colorectal Cancer Screening. V 2.2016.
October 20. Available at http://www.nccn.org.
12. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available
at http://www.nccn.org.
13. Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the
management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47. PMID:
23135763.
Last Updated on 10-Jan-2017
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