Have you ever heard of Lynch Syndrome and its connection to increased cancer risks?

Wondering what it is and how it can put you at a greater risk of having cancer?

In this blog, Karepedia will explore what Lynch Syndrome is, its genetic basis, the types of cancer it causes, and the importance of early detection and management.

Now, let’s delve into understanding Lynch Syndrome and the steps you can take to mitigate its cancer risks.

What Is Lynch Syndrome?

Lynch Syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is a genetic condition that increases the chance of developing certain types of cancer.

Here are some deets about Lynch Syndrome:

• Individuals with Lynch Syndrome face a significantly heightened risk of developing colorectal cancer.

• And an increased susceptibility to various other types of cancers, including endometrial, gastric, ovarian, small bowel, pancreatic, prostate, urinary tract, bile duct, sarcomas, brain cancers, and sebaceous tumours of the skin.

• Lynch Syndrome ranks among the most prevalent hereditary cancer syndromes, with estimates suggesting that approximately 1 in every 300 individuals may carry a genetic mutation associated with this condition.

• Identifying clues within a family's medical history, such as multiple diagnoses of colorectal, endometrial, ovarian, or other cancers on the same side of the family, can indicate the potential presence of Lynch syndrome.

• Cancers related to Lynch Syndrome often show a special pattern of mutations called microsatellite instability (MSI) or mismatch repair deficiency (MMR-D).

• Doctors suggest that those with colorectal cancer should get tested to check for MSI or MMR-D.

• Recent guidelines now recommend the same testing for all cases of endometrial cancer.

• Additionally, cancers linked with Lynch syndrome tend to be diagnosed at a younger age.

• Consequently, individuals with Lynch syndrome are at an increased risk of developing multiple types of cancers throughout their lifetime.

What Are the Signs of Lynch Syndrome?

• Doctors sometimes use a checklist called the revised Bethesda guidelines to figure out who should get tested for Lynch Syndrome. It includes:

• Having colorectal or endometrial cancer before age 50.

• Having colorectal or endometrial cancer, or another type of cancer, and tests show MSI or MMR-D.

• Getting colorectal cancer along with other cancers linked to Lynch Syndrome.

• Having a first-degree relative (like a parent, sibling, or child) who had colorectal cancer and another Lynch Syndrome-related cancer before age 50.

• Having colorectal cancer in two or more first- or second-degree relatives (like aunts, uncles, grandparents, grandchildren, nephews, or nieces) with another Lynch Syndrome-related cancer.

Lynch Syndrome And Its Types

The types of cancers associated with Lynch Syndrome include colorectal cancer, endometrial cancer, ovarian cancer, stomach cancer, small bowel cancer, ureter or renal pelvis cancer, bladder cancer, bile duct cancer, pancreatic cancer, and sebaceous adenomas of the skin. The definition of Lynch syndrome is still being refined.

Some individuals may have Lynch Syndrome even if their family history doesn't perfectly match the revised Bethesda guidelines.

Therefore, it's advisable for individuals with a family history suggesting the possibility of Lynch Syndrome to speak with a healthcare professional who specializes in genetic diseases and conditions.

Other variations of Lynch Syndrome include Muir-Torre syndrome, which occurs when individuals develop uncommon skin lesions or tumours such as sebaceous adenomas, sebaceous epitheliomas, sebaceous carcinomas, and keratocanthomas.

Since these skin lesions are more commonly observed in individuals with Lynch Syndrome, it is recommended that those diagnosed with such lesions undergo genetic evaluation by a trained healthcare professional.

Turcot syndrome is characterised by the development of brain tumours and colorectal cancers in affected individuals.

Historically, individuals with Lynch syndrome and/or familial adenomatous polyposis (FAP) were sometimes mistakenly diagnosed with Turcot syndrome. However, it is now understood that Turcot syndrome is not a distinct genetic syndrome.

What are the Causes of Lynch Syndrome?

• Lynch syndrome is primarily caused by genetic factors.

• This means that the risk of cancer can be inherited and passed down through generations within a family.

• These inherited mutations, also known as germline mutations, occur in genes responsible for DNA mismatch repair.

• The genes implicated in Lynch syndrome include MLH1, MSH2, MSH6, PMS2, and EPCAM.

• Mutations in any of these genes increase the lifetime risk of developing colorectal cancer, endometrial cancer, ovarian cancer, and other associated cancers.

How is Lynch Syndrome Diagnosed? BOX

• Lynch Syndrome diagnosis typically involves genetic testing conducted through a blood or saliva sample to analyse inherited DNA.

• This test identifies mutations in genes associated with Lynch syndrome, such as MLH1, MSH2, MSH6, PMS2, and EPCAM.

• However, it's important to note that not all families with Lynch syndrome will exhibit mutations in these genes.

• Additionally, screening tests on cancerous tissue can provide further insights. Microsatellite instability testing (MSI) and immunohistochemistry testing (IHC) are commonly recommended.

• Positive results from these screenings may prompt additional genetic testing to confirm Lynch syndrome.

Estimated Cancer Risks Associated with Lynch Syndrome

General Lifetime Cancer Risks for people with Lynch Syndrome:

• Colorectal cancer: 20% to 80%
• Stomach cancer: 1% to 13%
• Urinary tract (renal pelvis, ureter, bladder) cancer: 1% to 18%
• Small bowel cancer (intestines): 1% to 6%
• Pancreatic cancer: 1% to 6%
• Hepatobiliary tract cancer (liver/bile duct): 1% to 4%
• Brain or central nervous system tumour: 1% to 3%

Cancer Risks for Women with Lynch Syndrome

• Endometrial cancer: 15% to 60%
• Ovarian cancer: 1% to 38%

Solutions for Mitigating Lynch Syndrome

• Genetic Testing: Early detection through genetic testing can identify individuals with Lynch syndrome. Screening family members with a history of Lynch syndrome-associated cancers can help identify those at risk.

• Surveillance Programs: Regular screenings, such as colonoscopies, endoscopies, and imaging tests, can detect cancerous or precancerous lesions at an early stage. These screenings allow for timely intervention and treatment.

• Prophylactic Surgery: Some individuals with Lynch syndrome may choose to undergo prophylactic surgeries to reduce their cancer risk. For example, prophylactic removal of the colon (colectomy) or uterus (hysterectomy) may be considered in high-risk cases.

• Medication: Certain medications, such as aspirin, have shown potential in reducing the risk of colorectal cancer in individuals with Lynch syndrome. However, the use of medication for cancer prevention should be discussed with healthcare providers.

• Lifestyle Modifications: Adopting a healthy lifestyle, including regular exercise, maintaining a balanced diet, avoiding tobacco, and limiting alcohol consumption, can help reduce cancer risk in individuals with Lynch syndrome.

• Patient Education and Support: Providing education and support to individuals and families affected by Lynch syndrome is crucial. This includes raising awareness about the condition, facilitating access to genetic counselling, and offering emotional support throughout the screening and treatment process.