PROJECT SUMMARY/ABSTRACT
Alaska Native (AN) people have the highest recorded rate of colorectal cancer (CRC) in the world with twofold
higher incidence and mortality than US whites. This cancer disparity has persisted for over 30 years despite an
increase in AN CRC screening rates to levels similar to non-AN. A holistic approach to reducing CRC that
includes both primary and secondary prevention is vital. Yet, no epidemiological or cohort studies exist to
explain the increased risk of AN CRC. This will be the first cohort study to investigate the etiology of CRC
among AN people with the goal of identifying new risk factors with translational potential for primary prevention
and risk prediction. Additionally, as CRC risk is increasing among typically low-risk groups across the U.S.,
such as the young, understanding the causes of this disease in a population that has seen dramatic increases
in cancer risk over the past century may be more broadly informative. Led by the Alaska Native Tribal Health
Consortium (ANTHC), in partnership with the Fred Hutchinson Cancer Center (FHCC), this proposed research
will establish the first community-engaged cohort study of CRC risk among AN people. Building on our
successful pilot recruitment study, in Aim 1, we will enroll 1,000 individuals prior to colonoscopy screening in
Anchorage and three-four regional Tribal hospitals outside of Anchorage. The ultimate outcome of interest for
this study will include both incident CRC and advanced adenoma (adenomatous polyp ≥1 cm or containing
>25% villous component or high-grade dysplasia, or sessile serrated adenoma/polyp ≥1 cm). We will collect
exposome data using culturally appropriate and previously validated questionnaires on demographics, diet and
traditional food use, food storage and processing, medications, occupation, lifetime environmental exposures
and tobacco use. We will also collect medical history, including lifetime antibiotics and proton pump inhibitors,
and anthropometric information, as well as objective measures of physical activity and sleep, including
circadian rhythms. In Aim 2, we will collect biospecimens (tumor tissue, colon biopsies, saliva, hair, urine, and
blood), and biobank the samples as a resource for future work. Importantly, we already have IRB and Tribal
approval for future biospecimen testing including microbiome and epigenetics analyses. For Specific Aim 3, we
will conduct statistical analyses of these questionnaire, anthropometric, biomarker, and medical record data to
assess associations of risk factors with CRC. This study utilizes a community-based participatory research
approach to address a key health disparity of community concern. By establishing an AN cohort with unique
risk exposures we will gain a better understanding of CRC among this high risk population. This research will
provide critical information that can be used to inform future research, develop risk prediction models, and
design effective primary prevention strategies among AN people and other populations at high or increasing
risk of this disease.
