The overall goal of the Research Center is the creation of a research unit that can evaluate the complete colorectal cancer (CRC) screening process. The specific goal is the characterization of remediable failures of the two most commonly used screening tests (optical colonoscopy and fecal immunochemical tests [FIT]). Two important problems in CRC are over-screening and under-diagnosis: 1) >95% of people will not die of CRC, thus, for most patients, screening results only in worry & risk; yet 2) many CRC deaths occur despite CRC screening (i.e. in persons with prior screening). It is unclear how many deaths result from remediable failures of the screening process. Our center will evaluate a community-based cohort that includes detailed CRC screening and medical data for >2 million screening-eligible people/year; >10 years of data; large numbers of outcomes (38,000 cancers); geographic diversity (>35 medical centers across California); demographic diversity (140,000 African Americans, 320,000 Hispanics, and 200,000 Asian-Americans among current members); socioeconomic diversity; diversity of screening methods; access to tissue/cancer blocks; and a full spectrum of individual cancer risk. Project 1 will evaluate FIT, an effective and efficient noninvasive screening method. Project 2 will evaluate colonoscopy, a sensitive, widely used test that is the final common exam for all CRC screening strategies. Projects 1 & 2 will both evaluate patterns of use, especially: screening failures (cancers diagnosed despite screening); surveillance failures, and surveillance over-use. We will investigate physician and patient components for these failures using a recently developed systematic process that includes establishing bases for interventions that target barriers in health care settings. Project 1 will also evaluate clinically available genetic markers to evaluate for potential biological differences between FIT detected vs. screen failure cancers. Project 3 will model the effectiveness of colonoscopy vs. FIT utilizing community-based data from the full screening process acquired in Projects 1 & 2, in collaboration with a proven NCI consortium Cancer Intervention and Surveillance Modeling Network (CISNET) site, including different screening strategies for different patient populations, tailored to risk. The Center includes a trans-disciplinary group of researchers including gastroenterologists, oncologists, family physicians, population scientists, modeling experts, quality experts, behavioral experts, and experts in health care delivery. The Center can efficiently evaluate the full screening process and can provide substantial human, institutional, and patient resources for collaborative projects within the PROSPR network.