The American Cancer Society estimates that there will be over 150,000 new cases of rectal or colon cancer in 2024. Fortunately the rates of colorectal cancer have been slowly decreasing in older adults since the 1980s (though it is still on the rise in people younger than 55), and this is mainly due to an increase in cancer screening tests as well as changes in risk factors related to lifestyle choices. However, there is one form of hereditary colorectal cancer that is less connected to lifestyle choices: Lynch syndrome.

What Is Lynch Syndrome?

Lynch syndrome is one of the principal types of hereditary nonpolyposis colorectal cancer (HNPCC), an inherited condition that carries a predisposition to cancer of the rectum or colon. The two terms were once used interchangeably, but in recent years HNPCC has come to encompass a broader spectrum of hereditary disorders that represent an increased risk of colorectal cancer. Lynch syndrome (and HNPCC more broadly) are similar to familial adenomatous polyposis (FAP), but they involve mutations in different genes. Lynch syndrome is an autosomal dominant condition, meaning that a person only needs to inherit an altered gene from one parent to develop the syndrome.

People with Lynch syndrome have a higher-than-normal lifetime risk of developing colorectal cancer compared to the general population, but they also have generally higher risk of developing other types of cancer in different areas of the body. These include other cancers related to the gastrointestinal system like stomach cancer, bowel cancer, pancreatic cancer, and urinary tract cancer. Lynch syndrome-related cancers can also include skin cancer and brain cancer as well as cancers that affect the female reproductive system like endometrial cancer, uterine caner, and ovarian cancer.

There isn’t just one Lynch syndrome gene that can become mutated; in fact, there are several specific DNA mismatch repair genes (MMR) that under normal circumstances actually prevent mutation. But when these genes themselves are mutated, it compromises the body’s ability to protect against various types of cancer. Below are some of the genes involved in Lynch syndrome and the types of cancer they’re associated with:

  • MLH1: high risk of colorectal and endometrial cancer
  • MSH2: high risk of colorectal cancer and cancers of the gallbladder, bile ducts, pancreas, and small intestine
  • MSH6: high risk of endometrial cancer
  • EPCAM: high risk of endometrial and ovarian cancer
  • PMS2: elevated risk of cancer in the ovaries

What Causes Lynch Syndrome?

As a hereditary condition, the basic underlying cause of Lynch syndrome is gene mutation in one of the MMR proteins noted above. While this kind of mutation can happen to anyone, it is much more likely when a first-degree relative or other family member is already afflicted. Such mutations in these genes lead to microsatellite instability (MSI), a disruption in the stability of short, repeated sequences of nucleotides. Over time, an accumulation of unrepaired errors in the DNA can lead to tissue overgrowths like polyps that can eventually turn into cancer cells.

Signs and Symptoms of Lynch Syndrome

As Lynch syndrome is not itself a type of cancer but rather a predisposition to several types of cancer, it doesn’t have any specific signs or symptoms that can be clearly identified. However, there are a number of criteria (typically referred to as the Bethesda guidelines) that doctors of oncology use to determine which patients warrant further testing:

  • having colorectal or endometrial cancer before the age of 50
  • having one of the potential cancers with tissue that shows mismatch repair deficiency or microsatellite instability
  • having multiple related cancers at the same time
  • having family members who have Lynch syndrome or one or more related cancers

    Having Lynch syndrome does not necessarily mean a person will have cancer, and having one of the related cancers does not necessarily mean the person has Lynch syndrome. As with other types of cancer, research is still ongoing and the definition and characteristics of Lynch syndrome are still evolving.

    Diagnosis of Lynch Syndrome

    The diagnosis of Lynch syndrome can happen before, after, or at the same time as the diagnosis of one of the types of associated cancers. Sometimes a person can be evaluated for it based on the presence of the condition in a family member. It may also be tested for if a person has two of these types of cancers at the same time. In general, there are several common steps doctors will take if they suspect Lynch:

    • Family history: A healthcare provider will conduct a thorough clinical evaluation, taking into account the individual's personal medical history and family history of cancer.
    • Genetic counseling: For those with an already known family history of Lynch syndrome or related cancers, genetic counseling exists to provide the patient with information and guidance about how to proceed in light of having increased risk.
    • Endoscopy: Depending on the type of cancer and location in the body, an upper endoscopy or colonoscopy may be performed to assess the inner lining of the gastrointestinal tract. Any polyps or tumors found can be removed for biopsy to determine whether or not the tissue is cancerous.
    • MSI testing: Microsatellite instability testing is typically used on tumor tissue found during endoscopy. High levels of instability in DNA sequences are a strong indicator of defective mismatch repair and thus Lynch syndrome.
    • Genetic testing: Various types of genetic testing can be used in evaluating the DNA for mutations in the specific genes that are associated with Lynch syndrome. Immunohistochemistry (IHC) is one method that looks at the proteins related to MLH1, MSH2, etc. This kind of testing is typically done through blood samples.

    Treatment of Lynch Syndrome

    Since Lynch syndrome is defined by having a predisposition to colorectal and other cancers, it isn’t specifically the subject of treatment. Instead, the focus of treatment is on proactive management and surveillance to detect and address cancer at an early stage when it is far more likely to be treatable. This approach can involve several different strategies:

    • Surveillance and screening: People with Lynch syndrome are recommended to undergo regular screening for the associated cancers. For example, this can include colonoscopies for colorectal cancer or endometrial biopsies for endometrial or uterine cancer. The frequency of such screenings is generally higher than is recommended for the general population.
    • Lifestyle modification: While lifestyle factors are less likely to be determinative in Lynch syndrome, maintaining a balanced diet, engaging in regular physical activity, and avoiding tobacco and excessive alcohol consumption are likely to be beneficial for overall health and wellbeing.
    • Surgery: In some cases, people with Lynch syndrome may consider risk-reducing surgeries to remove organs at higher risk of cancer development. For example, a woman with Lynch syndrome may choose to undergo a risk-reducing hysterectomy to reduce the risk of endometrial cancer.

      Dedicated Digestive Care from Cary Gastro

      Lynch syndrome is fortunately fairly rare in the general population, so the average person doesn’t need to worry about it unless a family member has already been diagnosed or there are other signs of cancer. Nevertheless, the rates of colorectal cancer are only going down because of regular cancer screenings, and that is something everyone benefits from after the age of 45 (or earlier in some high risk patients). If you’d like to learn more about colorectal cancer screenings, please contact Cary Gastro to request an appointment.