Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited genetic condition that can significantly increase the risk of developing certain types of cancer. For instance, individuals with HNPCC have a 70-80% lifetime risk of developing colorectal cancer, while women with HNPCC have a 40-60% risk of developing uterine (endometrial) cancer. A parent with Lynch syndrome has a 50% chance of passing the condition on to each child.

Overall, this hereditary cancer predisposition syndrome is relatively rare, affecting approximately 1 in 279 individuals in the general population. HNPCC is linked to approximately 3% of colorectal cancers and 2% of endometrial cancers. However, not everyone who has Lynch syndrome will develop cancer.

What causes Lynch syndrome?

HNPCC is caused by an inherited mutation in one of several mismatch repair (MMR) genes, such as MLH1, MSH2, MSH6 or PMS2. MMR genes are responsible for correcting errors that occur when DNA is replicated during cell division. A mutated MMR gene can disrupt the normal DNA repair process, leading to an accumulation of genetic mutations that can result in cancer.

What are the risk factors for Lynch syndrome?

The primary risk factor for HNPCC is a family history of the condition or an associated cancer, particularly when diagnosed before age 50. These cancers include:

HNPCC is an inherited condition that cannot be controlled. However, when the condition is detected early, there are generally more opportunities to take preventative steps to reduce the risk of developing cancer.

Genetic counseling and testing may be recommended for an individual who has:

A family member with a confirmed diagnosis of Lynch syndrome
Colorectal cancer or endometrial cancer diagnosed at any age, particularly if pathology testing shows genetic alterations related to Lynch syndrome
Multiple primary cancer diagnoses
Several family members have been diagnosed with a type of cancer related to Lynch syndrome

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What are the signs and symptoms of Lynch syndrome?

HNPCC does not cause specific symptoms. Instead, it increases the risk of developing certain cancers, each of which has its own set of symptoms, such as:

Colorectal cancer – Abdominal pain, changes in bowel habits and rectal bleeding
Endometrial cancer – Pelvic pain and abnormal vaginal bleeding, especially after menopause
Ovarian cancer – Pelvic pain, abdominal bloating, changes in bowel habits and frequent urination
Stomach cancer – Abdominal pain, nausea, vomiting and indigestion

How is Lynch syndrome diagnosed?

The diagnostic process for HNPCC may include:

Medical history and assessment – While performing a detailed review of the patient’s personal and family medical history, the physician will look for patterns of cancer associated with Lynch syndrome, such as early-onset colorectal or endometrial cancer.
Genetic testing – A blood or saliva sample will be tested for MMR gene mutations.
Immunohistochemistry (IHC) screening – If the patient is diagnosed with colorectal or endometrial cancer, the tumor tissue may be tested for proteins synthesized by Lynch syndrome genes.
Microsatellite instability (MSI) screening – If the patient is diagnosed with colorectal or endometrial cancer, strands of DNA in the tumor tissue may show—based on their length—that the DNA mismatch repair process is not working well, an indication of Lynch syndrome.

How is Lynch syndrome treated?

HNPCC is not directly treated. Instead, treatment focuses on managing the increased cancer risk through regular surveillance, preventive measures and addressing any cancers that develop. For instance, individuals who are diagnosed with Lynch syndrome may be advised to have:

Frequent colorectal cancer screenings – Routine colonoscopies starting at age 20-25 and repeated every 1-2 years thereafter
Urinary tract and bladder testing – Periodic urinalyses and ultrasound scans to monitor for signs of blood or cancerous cells
Gastrointestinal cancer screenings – Endoscopies performed on the stomach and small intestine at a frequency recommended by a physician

Additionally, women who are diagnosed with Lynch syndrome may be advised to have:

Endometrial cancer screenings – An endometrial biopsy performed each year
Ovarian cancer screenings – An annual CA-125 blood test and transvaginal ultrasound (TVUS)

After thoroughly reviewing the potential risks and benefits, some individuals may choose to have preventative surgery to reduce their risk of developing cancer. For instance, women who are diagnosed with Lynch syndrome may opt to undergo a preventive hysterectomy and/or oophorectomy to remove the uterus and/or ovaries and reduce the risk of developing endometrial or ovarian cancer.

Benefit from world-class care at Moffitt Cancer Center

Moffitt’s genetic counseling and testing program is recognized as a specialty referral center by the Lynch Syndrome Screening Network (LSSN). The multispecialty team in our GeneHome clinic offers risk assessments, coordinates genetic testing, interprets genetic testing results and provides individualized education and genetic counseling. We also routinely follow individuals who are diagnosed with Lynch syndrome to help ensure they have access to the specialized expertise and cancer screenings they need.

If you would like to learn more about Lynch syndrome, you can request an appointment with a specialist in Moffitt’s Genetic Counseling Clinic by calling 1-813-745-8123 or sending an email message to genehome@moffitt.org. We do not require referrals.

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