Individualized screening decision tool for HNPCC Free

A58

For individuals at risk of colon cancer, determining the optimal period for and timing of screening exams can be difficult. Although formal guidelines exist for those at general risk, identifying those at elevated risk who are in need of increased screening is sometimes problematic. Hereditary colon cancer represents approximately 5% of cancers, and consist primarily of familial adenomatous poylposis (FAP) and hereditary non-polyposis colon cancer (HNPCC). For those with HNPCC, diagnosis may be difficult as the Amsterdam criteria is strict requiring a strong family history, and genetic testing of the DNA mismatch repair genes does not necessarily identify all mutations. Consequently, we have developed a personalized screening decision tool for at risk HNPCC patients that incorporates one's carrier probability based on family history. A microsimulation model is designed built upon the natural history disease states: healthy, adenoma, pre-clinical carcinoma, clinical carcinoma, and death. Based on SEER incidence rates, US census death rates, and sojourn time distributions for adenomas and carcinomas, transition rates for each state are estimated. From a patient's personal family history, gene carrier probabilities are estimated from MMRpro, a Mendelian gene carrier risk prediction model. Using these probabilities as weights for the various distributions, a cohort of simulated natural histories for the patient is generated. Varying intervals of screening are considered, and probabilities of early detection, late detection and over-diagnosis are then estimated according to the screening intervals. Our model was then piloted on a series of families who have undergone counseling at the Johns Hopkins hereditary colon cancer clinic.