Lynch syndrome (LS) is an inherited condition that increases the risk of certain cancers, particularly colorectal and endometrial cancers. It is caused by changes (mutations) in genes that normally help repair DNA errors. Without these repairs, cells can turn cancerous. LS is also called hereditary non-polyposis colorectal cancer (HNPCC).
Causes
- Inherited Mutation: LS follows an autosomal dominant pattern. You only need one copy of the mutated gene from either parent to have the condition.
- Genes Involved: MLH1, MSH2, MSH6, PMS2, or EPCAM. These genes normally fix DNA mistakes; mutations impair this process.
Cancer Risks
People with LS have a higher lifetime risk for:
- Colorectal cancer: 40–80% risk (vs. 4% general population).
- Endometrial (uterine) cancer: 40–60% risk.
- Other cancers: Ovarian (10–12%), stomach, urinary tract, liver, small intestine, brain (glioblastoma), and skin (sebaceous adenomas).
Cancers often occur at younger ages (e.g., colorectal cancer before 50).
Diagnosis
- Family History: Tools like Amsterdam II Criteria (multiple relatives with LS cancers across generations) or Bethesda Guidelines (early-onset cancers).
- Tumour Testing: Microsatellite instability (MSI) or immunohistochemistry (IHC) to check for DNA repair issues.
- Genetic Testing: Blood or saliva tests to confirm gene mutations.
Management & Prevention
Screenings:
- Colonoscopy: Every 1–2 years starting at 20–25 (or 5 years younger than the earliest family diagnosis).
- Endometrial/Ovarian: Annual pelvic exams, transvaginal ultrasound, and biopsy from age 30–35.
- Other: Upper endoscopy, urinary tests, or skin exams as needed.
Risk Reduction:
- Surgery: Prophylactic hysterectomy/oophorectomy (after childbearing).
- Medications: Aspirin* (e.g., 600 mg/day may lower colorectal cancer risk; discuss with your doctor).
- Lifestyle: High-fibre diet, limit red/processed meats, exercise, avoid smoking, and moderate alcohol.
Family Planning:
- Genetic counselling for relatives.
- Prenatal options (e.g., preimplantation genetic diagnosis).
Frequently Asked Questions
- Can LS be cured?
No, but risks can be managed with screenings and prevention.
- What if I test positive?
Work with your gynaecologist on a tailored plan; inform family members.
- Does LS skip generations?
No, but not everyone with the mutation develops cancer.
- Is genetic testing accurate?
Yes, but a negative test in families with LS still requires caution.
eGynaecologist Advice:
- You should seek gynaecological consultation if any member of your family has suffered associated cancers, particularly below the age of 50 years.
- You must consider risk reducing surgery and seek gynaecological consultation when you test positive for Lynch syndrome on genetic testing.
