Lynch Syndrome

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a rare genetic disorder that increases the risk of developing certain types of cancer, particularly colorectal cancer.

Causes and Risk Factors

Lynch syndrome is caused by mutations in one of several genes involved in DNA mismatch repair, including MLH1, MSH2, MSH6, PMS2, and EPCAM. These genes help to repair mistakes in DNA replication and recombination. When these genes are mutated, errors in DNA can accumulate, leading to cancer.

Types of Cancers Associated with Lynch Syndrome

Lynch syndrome increases the risk of developing several types of cancer, including:

• Colorectal cancer: The most common type of cancer associated with Lynch syndrome, with a lifetime risk of up to 80%.
• Endometrial cancer: Women with Lynch syndrome have a lifetime risk of up to 60% of developing endometrial cancer.
• Ovarian cancer: Women with Lynch syndrome have a lifetime risk of up to 20% of developing ovarian cancer.
• Stomach cancer: The lifetime risk of stomach cancer is increased in people with Lynch syndrome, particularly in those with a family history of the disease.
• Small intestine cancer: People with Lynch syndrome have an increased risk of developing small intestine cancer.
• Urinary tract cancer: Lynch syndrome also increases the risk of urinary tract cancer, including kidney and ureter cancer.
• Brain cancer: Some people with Lynch syndrome may be at increased risk of developing brain cancer, particularly glioblastoma.

Symptoms

The symptoms of Lynch syndrome are often the same as those of the associated cancers. For example:

• Colorectal cancer: Blood in the stool, changes in bowel habits, abdominal pain, and weight loss.
• Endometrial cancer: Abnormal vaginal bleeding, pelvic pain, and weight loss.
• Ovarian cancer: Pelvic pain, bloating, and difficulty eating or feeling full.

Diagnosis

Lynch syndrome is typically diagnosed through a combination of:

• Family medical history: A thorough family medical history can help identify a pattern of cancers that may be associated with Lynch syndrome.
• Genetic testing: Genetic testing can detect mutations in the genes associated with Lynch syndrome.
• Tumor testing: Tumor testing, such as microsatellite instability (MSI) testing and immunohistochemistry (IHC), can help identify tumors that are associated with Lynch syndrome.

Treatment and Management

The treatment and management of Lynch syndrome depend on the type of cancer diagnosed. In general, early detection and removal of precancerous polyps or tumors can help prevent the development of cancer.

• Colorectal cancer: Regular colonoscopies, starting at age 20-25, can help detect and remove precancerous polyps.
• Endometrial cancer: Annual endometrial biopsies, starting at age 30-35, can help detect abnormal cell growth.
• Ovarian cancer: Regular transvaginal ultrasounds and CA-125 blood tests, starting at age 30-35, can help detect ovarian cancer.

Prevention

There are several ways to reduce the risk of developing cancers associated with Lynch syndrome:

• Genetic counseling: Genetic counseling can help individuals understand their risk and make informed decisions about testing and management.
• Screening tests: Regular screening tests, such as colonoscopies and endometrial biopsies, can help detect cancer at an early stage.
• Risk-reducing surgery: In some cases, risk-reducing surgery, such as hysterectomy or colectomy, may be recommended to reduce the risk of developing certain cancers.

Frequently Asked Questions (FAQs)

What is Lynch syndrome?
Lynch syndrome is an inherited disorder that increases the risk of developing certain types of cancer.

Which cancers are associated with Lynch syndrome?
Cancers associated with Lynch syndrome include colorectal, endometrial, ovarian, stomach, small intestine, hepatobiliary, upper urinary tract, and brain cancers.

How is Lynch syndrome inherited?
Lynch syndrome is inherited in an autosomal dominant pattern, meaning a mutation in one of the two copies of the gene is sufficient to increase cancer risk.

What genes are associated with Lynch syndrome?
Mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes are associated with Lynch syndrome.

What are the symptoms of Lynch syndrome?
There are no specific symptoms of Lynch syndrome itself, but individuals may experience symptoms related to the development of associated cancers.

How is Lynch syndrome diagnosed?
Diagnosis of Lynch syndrome typically involves a combination of genetic testing, family history, and tumor testing.

What is the risk of cancer for individuals with Lynch syndrome?
The lifetime risk of developing colorectal cancer is approximately 20-80%, and the risk of endometrial cancer is approximately 20-60%.

Can Lynch syndrome be treated?
There is no treatment for Lynch syndrome itself, but early detection and removal of precancerous lesions can help prevent cancer development.

Are there any screening recommendations for individuals with Lynch syndrome?
Screening recommendations include regular colonoscopies, endometrial sampling, and other tests to detect cancer at an early stage.

Can genetic counseling help individuals with a family history of Lynch syndrome?
Yes, genetic counseling can help individuals understand their risk and make informed decisions about testing and screening.