My research program is focused on translational science in cancer prevention, most prominently risk stratification, early detection, and chemoprevention of gastrointestinal cancers. Major projects include the investigation of exposures associated with molecularly defined colorectal cancer subtypes, clinical evaluation of novel colorectal cancer screening technologies, and conduct of early phase chemoprevention trials. For example, using data and tissue resources from the population-based Iowa Women’s Health Study, our group recently reported that cigarette smoking was associated with increased risks for specific, molecularly-defined colorectal cancer subtypes (characterized by microsatellite instability, CpG island methylation, or BRAF mutation). These findings suggest that cigarette smoking may influence colorectal carcinogenesis through epigenetic modification, which has potential implications for novel behavioral intervention, early detection or chemoprevention strategies. Through support from the National Cancer Institute and the American College of Radiology Imaging Network, we also completed the largest prospective investigation reported to date of CT colonography as a primary colorectal cancer screening option. Compared to optical colonoscopy, CT colonography was found to have high sensitivity and specificity for screen-detecting large colorectal adenomas and cancers. These data have been prominently discussed in topic reviews and multi-society practice guidelines. In addition, our team provided the first report of a potentially beneficial chemopreventive intervention on esophageal squamous cell carcinoma in a randomized, controlled trial conducted in rural China. Through our unique, inter-disciplinary consortium (the Cancer Prevention Network), my group has also organized and activated other prospective trials for colorectal, esophageal, lung and multi-organ cancer chemoprevention, including the first-ever “phase 0” trial in preventive oncology.