The proposed research develops microsimulation models to examine the effect of screening as practiced on observed trends in colorectal cancer (CRC) incidence and mortality in a defined population of over 500,000 members of Group Health Cooperative (GHC), a large HMO in western Washington. Extensive information about this population is available from automated clinical data systems that capture multiple health care events, including dates and results of laboratory tests (FOBT) and endoscopy procedures, pharmacy utilization, outpatient physician visits and hospitalizations. An established link between GHC and the westem Washington SEER will be used to identify CRC cases in this defined population and a population-based registry of GI pathology will be used to identify non-malignant outcomes (e.g. advanced adenomas) among GHC members. The proposed research will address 3 primary aims: Aim 1: Develop a microsimulation model for colorectal cancer that describes natural history, screening, diagnosis, and mortality: The model we propose takes distributional functions as inputs for unknown parameters, rather than fixed values. The proposed model has at least four key advantages over previous strategies: 1) The model incorporates uncertainty in model inputs; 2) It allows incorporation of correlation between model parameters through their distributional forms; 3) Its use of distributions as inputs essentially automates sensitivity analyses and offers an important advantage over univariate sensitivity analysis; and 4) The model produces distributional estimates for outputs, quantifying their uncertainty. Aim 2: Model the effect of screening and polypectomy on the trends in CRC incidence and mortality within the Group Health Population aged 50 and older. Our model will use data describing dissemination of screening within this population, allowing us to examine the relationship between screening at GHC and trends in rates. Aim 3: Model the combined effect of HRT, screening and polypectomy on trends in CRC incidence within the female Group Health Population aged 50 and older. HRT has been shown to reduce the incidence and perhaps improve mortality from colorectal cancer. Our third aim will allow us to explore mechanisms for this reduction in risk, such as changes in the risks for adenomatous polyps, decreases in their transition to preclinical cancer, and lengthening of sojourn time.