From the Guidelines
Lynch syndrome is a genetic disorder that significantly increases the risk of developing certain types of cancer, particularly colorectal and endometrial cancer, and is characterized by mutations in DNA mismatch repair genes. It occurs due to mutations in genes such as MLH1, MSH2, MSH6, PMS2, or EPCAM, which normally help fix mistakes in DNA during cell division 1. When these genes don't function properly, errors accumulate in DNA, potentially leading to cancer development. People with Lynch syndrome have a significantly higher lifetime risk of colorectal cancer (up to 80%), endometrial cancer (up to 60% in women), and increased risks for cancers of the ovary, stomach, small intestine, urinary tract, brain, and skin 2. The condition follows an autosomal dominant inheritance pattern, meaning a person needs only one copy of the mutated gene to have the syndrome.
Key Characteristics and Risks
- Lifetime risk of colorectal cancer: up to 80%
- Lifetime risk of endometrial cancer in women: up to 60%
- Increased risks for other cancers, including ovarian, stomach, small intestine, urinary tract, brain, and skin cancers
- Autosomal dominant inheritance pattern
Diagnosis and Management
Genetic testing and counseling are crucial for diagnosis and for identifying family members who may also carry the mutation. If you have Lynch syndrome, you should undergo regular cancer screenings starting at a younger age than the general population, including:
- Colonoscopies beginning at age 20-25 and repeated every 1-2 years 3
- Regular gynecologic examinations with endometrial sampling for women
- Consideration of prophylactic gynecological surgery for female carriers who have completed childbearing or are postmenopausal 3
Importance of Early Detection and Prevention
Early detection and prevention strategies are critical in managing Lynch syndrome, as they can significantly reduce the risk of developing cancer and improve outcomes 4, 5. Regular screenings and genetic testing can help identify individuals with Lynch syndrome and allow for timely interventions to prevent or detect cancer at an early stage.
From the Research
Definition and Overview of Lynch Syndrome
- Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, is an autosomal-dominant inherited cancer susceptibility syndrome caused by a germline mutation in one of the DNA mismatch repair genes 6, 7.
- It is the most common cause of hereditary colon cancer, accounting for as much as 3% of all colon and endometrial cancers 7.
- Lynch syndrome is associated with early onset of cancer and the development of multiple cancer types, particularly colon and endometrial cancer 6, 7.
Cancer Risks Associated with Lynch Syndrome
- The lifetime cumulative risk of endometrial cancer for women with Lynch syndrome is 40% to 60%, which equals or exceeds their risk of colorectal cancer 6, 8.
- Women with Lynch syndrome also have an increased risk of ovarian cancer, with a lifetime risk of 6-8% 8.
- Lynch syndrome-associated endometrial cancers are primarily endometrioid, although non-endometrioid subtypes including clear cell, papillary serous and MMMT have been reported 8.
Screening and Prevention
- Current gynecologic cancer screening guidelines for women with Lynch syndrome include annual endometrial sampling and transvaginal ultrasonography beginning at age 30 to 35 years 6.
- Prevention options include the use of oral contraceptives, which are known to be highly effective for decreasing risk of both endometrial and ovarian cancer in the general population, and prophylactic surgery to remove the uterus and ovaries 8, 9.
- Risk-reducing hysterectomy and bilateral salpingo-oophorectomy (RRHSO) has been shown to be a cost-effective form of management and prevention of gynecological malignancies in patients with Lynch syndrome 9.