Although some debate continues over the precise strength of the scientific evidence, there remains a strong consensus that habitual consumption of processed meat is a prominent causal risk factor for colorectal cancer (CRC). Two recent systematic reviews have concluded that each additional 50 gram serving/day of processed meat conveys an 18-23% increased risk, a figure highly relevant to U.S. adults whose mean daily consumption of processed meat is 50-60 grams. Substituting a modest proportion of that meat with an alternative protein source with lesser risk could therefore have a major impact on reducing the societal burden of CRC. Although an important protein source in many cultures for centuries, only recently have select insect species begun to gain traction as an acceptable protein source in North America. Cricket powder, comprised of ground, whole roasted crickets, can be incorporated into many foodstuffs with little or no discernible change in taste, making it an excellent candidate for acceptance in a culture naïve to entomophagy. Moreover, not only is its protein content very high, but qualitatively it is a complete protein. Further, cricket powder’s unique array of physiochemical features indicate it may possess cancer-preventive properties. Nevertheless an examination of insect-based foodstuffs for the purpose of cancer prevention has never before been explored, so the scope of this exploratory proposal is highly consistent with the spirit of the R03 mechanism. Achieving protein requirements through entomophagy has the further advantage of promoting sustainable agriculture, a longstanding goal of the U.S. Department of Agriculture. We hypothesize that in a well-accepted animal model of CRC, tumorigenesis will be diminished by a diet whose protein is largely derived from cricket powder compared to one whose protein is derived from processed meat, and will be non-inferior to the tumorigenesis observed with diets whose protein is derived from the conventional non-meat sources, dairy and soy. Our long-term goal is to identify a novel approach to CRC prevention that is effective, non-invasive, welltolerated, and low cost, and thus will have wide application both domestically and globally. A secondary longterm goal is to promote sustainable food systems. We propose to conduct a study in a murine model of obesitypromoted colorectal carcinogenesis to: 1) determine whether substitution with cricket powder attenuates the enhanced risk of colorectal neoplasia that accompanies the habitual consumption of processed meat, 2) examine whether tumorigenesis generated by a cricket powder-based diet is non-inferior to diets whose protein is derived from soy flour or whole milk solids, and 3) begin to delineate the biochemical, molecular, and cytokinetic pathways by which a cricket-powder based diet generates less tumorigenesis than a processed meat one. My laboratory has successfully pursued a wide array of research topics in the nutritional chemoprevention of colorectal carcinogenesis in various animal models for over 25 years, providing us with all the necessary expertise to conduct the proposed study expeditiously and with scientific rigor.