The relationship between the BRAF p.V600E mutation and a family history of CRC in the early-onset CRC cases from the Australasian Colon Cancer Family Study

Background The BRAF p.V600E somatic mutation is present in approximately 10-20% of unselected colorectal cancer (CRC) and 30% -75% of CRCs demonstrating high levels of microsatellite instability (MSI-H). Currently, testing for the BRAF p.V600E mutation is undertaken to exclude Lynch syndrome in MSI-H CRCs that demonstrate loss of the MLH1 and PMS2 proteins by IHC. However, recent evidence suggests that the BRAF p. V600E mutation is associated with a familial predisposition to serrated neoplasia, an increased risk of CRC and possibly extra-colonic cancers in relatives. The aim of this study was to determine 1) if early-onset CRC with the BRAF p.V600E mutation is associated with a family history of CRC, and 2) if pathological features of BRAF positive CRCs associate with CRC development in relatives.