Alaska Native (AN) people have among the highest rates of colorectal cancer (CRC) recorded globally. Preventing CRC is an important health priority of AN tribal health leaders and communities. Lifestyle and genetic risk and protective factors for CRC among AN people remain understudied. We have been working to establish a tribally led, community-based, comprehensive investigation of lifestyle and genetic risk and protective factors for CRC among AN people. We describe the process of initiating this research study, including conversations with key tribal health system staff. We discuss themes that arose during these conversations and literature review and describe how those themes were used during the study design and protocol development phase. This description is intended to provide guidance to other researchers working to establish community-based studies of cancer risk, particularly among tribal communities.