COMBINED USE OF MOLECULAR AND BIOMARKERS FOR PRESYMPTOMATIC CARRIER RISK ASSESSMENT IN FAMILIAL ADENOMATOUS POLYPOSIS - IMPLICATIONS FOR SCREENING GUIDELINES

Predictive carrier testing for the inherited disorder of familial aden omatous polyposis (FAP) can be conducted using DNA markers linked to t he FAP locus. The presence of characteristic hypertrophic retinal lesi ons has been advocated as useful biomarkers for FAP. We have compared molecular linkage and retinal screening techniques by evaluating the p resymptomatic carrier risk of 40 at-risk individuals from 15 FAP famil ies. Linkage analysis was informative in all and retinal lesion analys is in 25 cases. For informative at-risk population, predictive diagnos is by both techniques was completely concordant and identified 15 memb ers at ''high'' and 10 at ''low'' risk of inheriting FAP. Because of t he unique advantages offered by each technique, a strategy integrating both techniques will increase the number of FAP families that can be screened presymptomatically. Identification of individuals at high ris k of polyposis will improve their clinical surveillance and further re duce the incidence of colorectal cancer in FAP families.