Cancer Risks Are Lower in Lynch Syndrome Families with MSH6 Mutations

Lynch syndrome is an autosomal dominant disorder that accounts for about 3% of colorectal cancers, as well as increased risks for endometrial, ovarian, small bowel, urethral, and gastric cancers. Affected patients carry germline mutations in one of four mismatch-repair mutations of genes MLH1, MSH2, MSH6, and PMS2. Previous studies have suggested that overall cancer risks are lower in patients carrying MSH6 mutations than MLH1 or MSH2. However, these studies might have overestimated risks because of selection and ascertainment biases.

Now, researchers have estimated age-specific cumulative risks for these cancers in 537 families enrolled from 40 cancer genetics clinics in France, including 248 with MLH1, 256 with MSH2, and 33 with MSH6. The …