From the Guidelines
Individuals with MSH6 mutations should undergo colonoscopy every 2 years starting at age 35 to manage their increased risk of colorectal cancer. This recommendation is based on the most recent guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG) 1. The guidelines suggest that MSH6 and PMS2 pathogenic variant carriers should have different ages of onset for colorectal surveillance, with MSH6 carriers starting at age 35.
The decision to perform colectomy should be made on an individual basis, taking into account patient factors and preferences, as well as the risk of metachronous CRC, age, and the patient's preparedness to continue colonoscopic surveillance 1. It is essential to provide high-quality patient information and facilitate shared decision-making between the patient and surgeon.
The cancer risk associated with MSH6 mutations tends to develop at a later age compared to other Lynch syndrome genes, with a reported average age at first diagnosis of 54 years 1. Individuals with MSH6 mutations have an elevated lifetime risk of colorectal cancer, endometrial cancer in women, and increased risks for other cancers. Genetic counseling is crucial for individuals with MSH6 mutations and their family members, as this condition follows an autosomal dominant inheritance pattern.
Key points to consider in the management of MSH6 mutations include:
- Colonoscopy every 2 years starting at age 35
- Individualized decision-making regarding colectomy
- Genetic counseling for affected individuals and their family members
- Screening for other associated cancers
- Consideration of patient factors and preferences in management decisions 1.
From the Research
MSH6 Mutation Overview
- MSH6 mutations are associated with hereditary nonpolyposis colorectal cancer (HNPCC) and Lynch syndrome, which increase the risk of developing certain types of cancer, including colorectal, endometrial, and ovarian cancer 2, 3, 4, 5, 6
- The cumulative risk of developing cancer in MSH6 mutation carriers varies by age and sex, with men having a higher risk of colorectal cancer and women having a higher risk of endometrial cancer 2, 6
Cancer Risk in MSH6 Mutation Carriers
- The cumulative risk of colorectal cancer in MSH6 mutation carriers is lower than in MLH1 and MSH2 mutation carriers, with a risk of 54% for men and 30% for women by age 70 6
- The cumulative risk of endometrial cancer in female MSH6 mutation carriers is higher than in MLH1 and MSH2 mutation carriers, with a risk of 61% by age 70 6
- The age of onset for colorectal and endometrial cancer is delayed in MSH6 mutation carriers compared to MLH1 and MSH2 mutation carriers 3, 4, 6
Surveillance and Management
- Surveillance colonoscopy starting at age 30 years is recommended for female MSH6 mutation carriers, instead of 20-25 years 2, 6
- Prophylactic hysterectomy may be more indicated in female MSH6 mutation carriers compared to MLH1 and MSH2 mutation carriers 6
- Individuals with MSH6 mutations could be offered cancer surveillance from a later age, and those with truncating MLH1 mutations could begin endometrial cancer surveillance later than those with nontruncating mutations 4