Mismatch repair cancer syndrome

Autosomal recessive - en

Mismatch repair cancer syndrome (MMRCS), also known as Lynch syndrome, is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon and rectum, which are collectively referred to as colorectal cancer. This syndrome is caused by mutations in genes responsible for the DNA mismatch repair (MMR) system, which is crucial for correcting errors that occur during DNA replication.

Genetics

MMRCS is typically inherited in an autosomal dominant manner, meaning that a mutation in just one of the two copies of the gene is sufficient to increase cancer risk. The primary genes involved in MMRCS include MLH1, MSH2, MSH6, and PMS2. Mutations in these genes impair the MMR system, leading to an accumulation of errors in the DNA, which can result in uncontrolled cell growth and cancer.

Associated Cancers

Individuals with MMRCS have a significantly increased risk of developing several types of cancer, including:

• Colorectal cancer
• Endometrial cancer
• Ovarian cancer
• Gastric cancer
• Small intestine cancer
• Hepatobiliary cancer
• Urinary tract cancer
• Brain cancer
• Skin cancer

Diagnosis

Diagnosis of MMRCS typically involves a combination of family history assessment, genetic testing, and tumor testing. Genetic testing can identify mutations in the MMR genes, while tumor testing can reveal microsatellite instability (MSI) or loss of MMR protein expression, both of which are indicative of MMR deficiency.

Management

Management of MMRCS involves regular surveillance and screening for early detection of cancers. This may include:

• Regular colonoscopy starting at an earlier age than the general population
• Annual or biennial endometrial biopsy for women
• Consideration of prophylactic surgeries, such as colectomy or hysterectomy, in certain high-risk individuals

Prevention

Preventive measures for individuals with MMRCS may include lifestyle modifications, such as maintaining a healthy diet, regular exercise, and avoiding smoking. Additionally, chemoprevention with aspirin has been shown to reduce the risk of colorectal cancer in some individuals with MMRCS.

See Also

• Colorectal cancer
• Genetic testing
• Microsatellite instability
• Autosomal dominant
• DNA mismatch repair