From the Guidelines
Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant genetic disorder characterized by an increased risk of developing colorectal, endometrial, ovarian, and other cancers 1.
Key Characteristics
- Individuals with Lynch syndrome have an estimated lifetime cumulative incidence of colorectal cancer up to 80% and endometrial cancer up to 60% 1
- They also have increased risks of other cancers, including stomach, small intestine, pancreas, biliary tract, ovary, urinary tract, and brain 1
Diagnosis and Management
- Screening for genetic mutations, such as Lynch syndrome, should be considered in all patients with endometrial (and colorectal) cancer, but especially in those younger than 50 years 1
- Tumor testing with IHC for MMR proteins and/or MSI is recommended in individuals with CRC 1
- Full germline genetic testing should include DNA sequencing and large rearrangement analysis 1
- Follow-up recommendations in mutation carriers include colonoscopy every 1–2 years and gynaecological examination on a yearly basis from age 30 to 35 years 1
- Prophylactic gynaecological surgery might be an option for female carriers who have completed childbearing or are postmenopausal 1
- Aspirin therapy has been shown to reduce the risk of colorectal cancer in individuals with Lynch syndrome, and is typically recommended for a duration of at least 2 years 1
Surveillance and Prevention
- Individuals with Lynch syndrome are recommended to undergo regular surveillance to detect cancers early and prevent them from developing 1
- Annual colonoscopy starting at age 20-25 is recommended for individuals with Lynch syndrome 1
- Prophylactic hysterectomy and bilateral salpingo-oophorectomy should be considered after childbearing is complete 1
From the Research
Definition and Prevalence of Lynch Syndrome
- Lynch syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is an autosomal dominant syndrome that accounts for 2-5% of all colorectal cancer cases 2, 3, 4, 5, 6.
- It is caused by a mutation in one of the DNA mismatch repair genes, such as hMSH2, hMLH1, MSH6, or PMS2 2, 3, 4, 5.
- The prevalence of Lynch syndrome in the general population is estimated to be around 1 in 500 3.
Clinical Characteristics and Risks
- Patients with Lynch syndrome develop colorectal carcinoma at an early age, with a lifetime risk of 70-80% 4.
- They also have an increased risk of developing other cancers, including endometrial, ovarian, stomach, small bowel, hepatobiliary tract, ureter, and renal pelvis cancers 2, 3, 4, 5.
- The prognosis for patients with Lynch syndrome is better than for those with sporadic colorectal cancer, and systematic surveillance and treatment can help detect cancers at an earlier stage and improve prognosis 2, 3.
Diagnosis and Management
- Diagnosis of Lynch syndrome typically involves a two-step process, including analysis of tumor tissue for evidence of deficient mismatch repair and genetic testing for mutations in the DNA mismatch repair genes 3.
- Genetic counseling and surveillance for high-risk family members should begin at age 25, and include annual colonoscopy and fecal occult blood testing 2.
- Selective literature review suggests that systematic colonoscopic surveillance can reduce the risk of colorectal cancer and improve prognosis 3.