ABSTRACT Almost nothing is known about the prevalence of comorbidities among American Indian and Alaska Native (AIAN) cancer survivors, and how comorbidities impact cancer treatment and survival in this population. Yet, AIAN people have higher incidence of several potential comorbid conditions, relative to their non-Native counterparts. Comorbidities impact the clinical management of cancer, including which cancer treatments a patient receives and when they receive that treatment. As a result, cancer patients with comorbidities are more likely to have poorer survival and quality of life than their comorbidity-free counterparts. There is a critical need to understand prevalence and impact of comorbidities on cancer treatment and outcomes among AIAN people; without this information, our ability to address known cancer disparities in this underserved minority population will remain limited. The objective of this research is to understand the landscape of comorbidities among AIAN cancer patients, and how they influence cancer treatment and survival. The central hypothesis is that comorbidities play a central role in the undue burden of cancer among AIAN people. The rationale for this study is that understanding the prevalence of comorbidities among AIAN cancer patients, and how they impact cancer treatment delivery and outcomes, will provide critical opportunities for multi-level intervention targeting health systems, providers, and/or patients. This research supports a long-term goal to reduce the burden of cancer among AIAN people by reducing the impact of comorbidities on treatment and survival. To address this objective, this research will pursue three specific aims, and one exploratory aim. The specific aims will use the SEER-Medicare linked database to 1) Determine the prevalence of comorbidities among AIAN people aged over 65y; 2) Determine impact of comorbidities on receipt of timely and evidence- based services during diagnosis, staging and first-line treatment among AIAN people aged over 65y; and, 3) Evaluate impact of comorbidities on cancer survival among AIAN people aged over 65y. An exploratory aim will determine the feasibility of reproducing these analyses in the Indian Health Service (IHS) National Patient Information Reporting System (NPIRS) data warehouse. This research is innovative because it uses underutilized datasets to explore questions about which nothing is known for AIAN people. Further, we propose a community engaged approach to this secondary data analysis that will inform this and future work. Upon the successful completion of this research, the role that presence and number of comorbidities plays in cancer diagnosis, treatment, and survival among AIAN people will be known. This information will provide critical information to understand causes of AIAN cancer disparities that will be used to drive future healthcare-based structural and programmatic interventions.