Founder mismatch repair mutation common in hereditary colorectal cancer

A mutation in a mismatch repair gene seems to be frequent and widespread throughout the U.S. in patients with hereditary nonpolyposis colorectal cancer (HNPCC), a new report suggests. Study authors recommend that individuals at risk for HPNCC be screened for this particular mutation, known as MSH2.

“Routine testing of subjects with a family history could identify individuals who should be targeted for early detection and prevention efforts,” study co-author Stephanie M. Coronel told Reuters Health.HPNCC is believed to account for up to 7% of the worldwide incidence of colorectal cancer, lead author Dr. Henry T. Lynch, at Creighton University School of Medicine in Omaha, Nebraska, and colleagues note in their article, published in the Journal of the American Medical Association for February 11. HPNCC is associated with inherited mutations in mismatch repair genes.Dr. Lynch’s team has identified nine families that share the identical deletion of exons 1 through 6 of the MSH2 gene. DNA testing of 137 family members revealed that there were 61 carriers, residing in 14 states.Genealogical studies helped them establish a 13-generation lineage traced back to a single couple who emigrated from Germany in the early 1700s.Based on their calculations, “10% to 15% of HPNCC families may have this mutation,” Coronel said.”We hope to work with other genetic centers to look for additional families so we can better characterize [the syndrome] and get a better handle on the mutation’s prevalence,” she said. “If it as common as we think, testing for it could become the first step to genetic testing instead of doing the full sequencing right away.”Currently, the group at Creighton University and collaborators at Ohio State University in Columbus, Ohio are set up to perform the assay.(Source: JAMA 2004;291:718-724: Reuters Health: Karla Gale: February 11, 2004: Oncolink)