Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited cancer syndrome that increases the risk of various types of cancer. This syndrome arises due to mutations in DNA repair genes, significantly increasing the risk of colorectal and endometrial (uterine) cancer. Lynch syndrome exhibits autosomal dominant inheritance, meaning there is a 50% chance of passing the mutation to the offspring if one parent carries it. Genetic counseling, family member evaluation, and psychological support play a significant role in managing the syndrome.
What Causes Lynch Syndrome?
Lynch syndrome is caused by hereditary mutations in DNA repair genes:
Mutations in DNA Repair Genes: Lynch syndrome results from mutations in DNA repair genes such as MLH1, MSH2, MSH6, PMS2, and EPCAM, which correct microsatellite instability. These mutations prevent the repair of DNA errors, leading to cancer development.
Autosomal Dominant Inheritance: Lynch syndrome exhibits autosomal dominant inheritance, meaning a parent carrying the mutation has a 50% chance of passing it to their children.
Microsatellite Instability (MSI): Microsatellites are short, repeating sequences in DNA. MSI occurs when DNA repair genes fail to correct errors in these sequences properly.
De Novo Mutations: In rare cases, Lynch syndrome can arise from a new mutation not previously seen in the family.
What Are the Symptoms of Lynch Syndrome?
People with Lynch syndrome have an increased risk of various types of cancer, but the most common are:
- colorectal cancer
- endometrial cancer
- ovarian cancer
- stomach cancer
- small intestine cancer
- urinary system cancers
- brain and central nervous system cancers
- skin cancers
How Is Lynch Syndrome Diagnosed?
Doctors diagnose Lynch syndrome using clinical criteria, molecular tests, and genetic tests:
Family History: Evaluating the presence of early-onset colorectal cancer or other cancers associated with Lynch syndrome in the family.
Amsterdam Criteria: The presence of colorectal cancer in three or more family members, cancer in two generations, and cancer development in one person before age 50 are used in diagnosing Lynch syndrome.
Bethesda Criteria: Testing patients diagnosed with colorectal cancer at a specific age or with particular histological features.
Microsatellite Instability (MSI) Testing: Used to assess the presence of MSI in tumor tissue.
Immunohistochemistry (IHC): Used to examine the expression of DNA repair proteins (MLH1, MSH2, MSH6, PMS2) in tumor tissue.
DNA Analysis: Blood samples are used to analyze DNA to detect mutations in MSH2, MLH1, MSH6, PMS2, and EPCAM genes.
Sequencing: Genetic sequencing methods are used to identify specific gene mutations.
Sample Collection: Blood and tumor tissue samples are collected from the patient.
Laboratory and Imaging Analysis: The collected samples undergo molecular tests and genetic analyses.
Evaluating Results: Diagnosis is made by combining clinical symptoms, family history, molecular, and genetic test results.
How Is Lynch Syndrome Treated?
The treatment and management of Lynch syndrome focus on reducing cancer risk, early diagnosis, and treatment:
Colonoscopy: Starting from ages 20-25 or 2-5 years after diagnosis, colonoscopy should be performed every 1-2 years.
Endometrial Cancer Screening: Regular screening should be done using transvaginal ultrasound and endometrial biopsy.
Ovarian Cancer Screening: Regular screening may be recommended using transvaginal ultrasound and blood tests (CA-125).
Stomach Cancer Screening: Stomach cancer screening can be done using gastroscopy, especially in high-risk areas.
Urinary System Cancer Screening: Urine cytology and renal ultrasound screenings may be recommended.
Skin Examination: Regular dermatological examinations should be done for skin cancers.
Colorectal Cancer: Prophylactic colectomy (removal of the colon) may be considered for high-risk patients.
Endometrial and Ovarian Cancer: Prophylactic hysterectomy and oophorectomy may be considered for women who have completed their childbearing plans.
Aspirin: Low-dose aspirin may be recommended to reduce cancer risk. However, it is important to consult a doctor about aspirin use.
Surgical Intervention: Surgery may be performed if cancer is detected.
Chemotherapy and Radiotherapy: Chemotherapy and radiotherapy may be used depending on the type and stage of cancer.
Family Member Evaluation: Genetic testing is recommended for family members of individuals diagnosed with Lynch syndrome.
Risk Assessment: Providing information to family members about the disease and assessing future risks.
Psychological Counseling: Psychological support should be provided to patients and their families to cope with cancer risk and improve quality of life.
Support Groups: Participation in support groups should be encouraged for sharing experiences with individuals in similar situations.
Healthy Diet and Exercise: A healthy diet and regular exercise are recommended to improve overall health.
Avoiding Smoking and Alcohol: Avoiding factors that can increase cancer risk.
Initial Evaluation: After diagnosis, a comprehensive evaluation of all symptoms and the patient’s health status is conducted.
Individual Treatment Plan: A personalized treatment plan is created for each patient based on factors such as age, general health status, current symptoms, and cancer risk.
Implementation and Monitoring: Selected treatment methods are implemented, and the effectiveness of the treatment is regularly monitored.
How Should Lynch Syndrome Be Managed?
The management of Lynch syndrome focuses on reducing cancer risk, early diagnosis, and treatment. Therefore, it requires a multidisciplinary approach:
Colonoscopy: Starting from ages 20-25 or 2-5 years after diagnosis, colonoscopy should be performed every 1-2 years. This is important for detecting colorectal cancer at an early stage.
Endometrial Cancer Screening: Regular screening should be done for women using transvaginal ultrasound and endometrial biopsy.
Ovarian Cancer Screening: Regular screening may be done for women using transvaginal ultrasound and CA-125 blood test.
Stomach Cancer Screening: Stomach cancer screening can be done using gastroscopy, especially in high-risk areas.
Urinary System Cancer Screening: Urine cytology and renal ultrasound screenings may be recommended.
Skin Examination: Regular dermatological examinations should be done for skin cancers.
Colorectal Cancer: Prophylactic colectomy (removal of the colon) may be considered for high-risk patients.
Endometrial and Ovarian Cancer: Prophylactic hysterectomy and oophorectomy may be considered for women who have completed their childbearing plans.
Aspirin: Low-dose aspirin may be recommended to reduce cancer risk. However, it is important to consult a doctor about aspirin use.
Family Member Evaluation: Genetic testing is recommended for family members of individuals diagnosed with Lynch syndrome.
Risk Assessment: Providing information to family members about the disease and assessing future risks.
Psychological Counseling: Psychological support should be provided to patients and their families to cope with cancer risk and improve quality of life.
Support Groups: Participation in support groups should be encouraged for sharing experiences with individuals in similar situations.
Healthy Diet and Exercise: A healthy diet and regular exercise are recommended to improve overall health.
Avoiding Smoking and Alcohol: Avoiding factors that can increase cancer risk.
Multidisciplinary Approach: Close collaboration between healthcare professionals from different specialties such as dermatologists, oncologists, endocrinologists, gastroenterologists, genetic counselors, and psychologists should be ensured.
Regular Consultations: Consultations from other specialties should be obtained when necessary.
Initial Evaluation: After diagnosis, a comprehensive evaluation of all symptoms and the patient’s health status is conducted.
Individual Treatment Plan: A personalized treatment plan is created for each patient based on factors such as age, general health status, current symptoms, and cancer risk.
Implementation and Monitoring: Selected treatment methods are implemented, and the effectiveness of the treatment is regularly monitored.