Overview

Purpose: The MSH2 test is often performed to assess the risk of hereditary cancers, particularly Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC). Lynch syndrome is associated with mutations in mismatch repair genes, including MSH2.

Indications for Testing:

• Family history of colorectal cancer or other cancers associated with Lynch syndrome.
• Personal history of colorectal cancer, particularly at a young age.
• Identification of cancer characteristics suggestive of Lynch syndrome.

Risk Assessment

Normal Function: The MSH2 gene encodes a protein that plays a critical role in repairing DNA errors that occur during cell division. Proper function helps prevent mutations that could lead to cancer.

Increased Risk: Mutations in MSH2 can impair DNA repair, increasing the likelihood of developing cancers such as colorectal cancer, endometrial cancer, and other cancers associated with Lynch syndrome.

Risk Assessment:

• Positive Result: If a mutation is detected in the MSH2 gene, it suggests an increased risk for Lynch syndrome and associated cancers. This may prompt further evaluations, such as surveillance for early cancer detection and possibly preventive measures.
• Negative Result: A negative result indicates no detected mutations in MSH2. However, it doesn’t completely rule out the presence of Lynch syndrome or other genetic conditions if clinical symptoms or family history suggest otherwise.

Normal Range

Normal Range: In the context of genetic testing, a “normal” result means that no pathogenic mutations in the MSH2 gene have been found. The interpretation is based on identifying whether or not the specific gene variants associated with increased cancer risk are present.

Interpretation

Pathogenic Mutations: If a mutation is identified, it is usually classified based on its potential impact:

• Pathogenic: Known to increase cancer risk.
• Likely Pathogenic: Likely to increase cancer risk but with less certainty.
• Variants of Uncertain Significance (VUS): Unknown impact on cancer risk.

Negative or Non-Pathogenic Result: No mutations are found in the MSH2 gene, suggesting no increased risk from this gene alone, though it doesn’t eliminate the possibility of other genetic or environmental risk factors.

Sample Type

Sample Type: The MSH2 test typically requires a sample of DNA, which can be collected via:

• Blood Sample: Most commonly used, obtained through a standard blood draw.
• Saliva Sample: Sometimes used for genetic testing, though less common.
• Buccal Swab: A swab of the inside of the cheek, used to collect cells for DNA analysis.