Value of predictive genetic testing in management of hereditary non-polyposis colorectal cancer (HNPCC)

Objective: To investigate the impact of predictive genetic testing on colon oscopic surveillance in an extended family with hereditary non-polyposis co lorectal cancer (HNPCC). Setting: Familial Bowel Cancer Service, The Royal Melbourne Hospital, Victo ria. Subjects: 96 people registered with the Service who were apparently unaffec ted members of an extended family that met the classic Amsterdam criteria f or HNPCC and carried an MLH1 gene mutation (1VS9+3insT). Intervention: Predictive genetic testing was offered in a cascade manner to at-risk family members; mutation-positive individuals were advised to have annual colonoscopic surveillance, while mutation-negative individuals were withdrawn from surveillance. Main outcome measures: Previous compliance with recommended colonoscopic su rveillance; uptake and results of genetic testing; expected effect of genet ic test results on number of colonoscopies over five years. Results: 22 of the 96 family members (23%) were not complying with recommen ded surveillance. Of 48 individuals offered predictive genetic testing, 41 (85%) responded and 39 (81%) underwent testing. Seven of the 39 (18%) were positive for the family-specific mutation, and 32 (82%) were negative. The 39 tested individuals and 37 of their descendants who were registered with the screening program had undergone 70 colonoscopies in the five years befo re genetic testing. In the five years after testing, only 37 surveillance c olonoscopies were planned (annual or two-yearly colonoscopies for the six m utation-positive individuals and five-yearly colonoscopies for four mutatio n-negative individuals with previously identified adenoma), an almost 50% r eduction in colonoscopies. Conclusion: Predictive genetic testing in HNPCC families allows many indivi duals to be withdrawn from regular colonoscopic surveillance. It may theref ore reduce costs, as well as have emotional benefits for many individuals.