Abstract PL03-05: A framework for community-engaged participatory research in cancer genomic sequencing: A collaborative with sovereign tribal nations in the American southwest
Authors: Willman Cheryl L. 
Published: June 2022

Abstract
While American Indian Tribes and communities are highly diverse in ethnicity, language, and culture, there is one unfortunate characteristic they share: profound cancer health disparities. Compounded by low rates of cancer screening and more limited access to healthcare, American Indians are more often diagnosed at later stages of disease and have the poorest outcomes in all types of cancer when compared to any other racial and ethnic group in the United States (Jamal et al. JNCI 2017; Sep; 109(9)). American Indians and Alaskan Natives (AI/AN) across the U.S. are impacted by a significantly higher incidence of several cancers when compared to non-Hispanic Whites (NHW): hepatocellular carcinoma; renal cell carcinoma; and cancers of the biliary tree (gall bladder and cholangiocarcinoma). In terms of mortality, AI/AN have the nation’s highest rate of death from liver cancer (2.2-fold &gt; NHW) and a 1.9-fold higher rate of death from kidney cancer. The incidence of colorectal cancer in AI/AN communities has also increased significantly.
The cause of these significant cancer disparities is undoubtedly multifactorial. In addition to low rates of cancer screening, other contributing factors include differences in access to healthcare and timely interventions; distinct cultural perspectives and beliefs regarding cancer etiology, screening, and treatment; differences in diet, obesity, metabolism, and risk behaviors (including tobacco, alcohol, and intravenous drug use); variable rates of vaccination and treatment for Hepatitis, HPV, and other viruses; ancestry-related biologic and genetic factors; and differences in environmental exposures. In the American Southwest, exposure of Tribal communities to environmental and carcinogenic toxins, including exposure to toxins such as aristolochic acid and aflatoxin, and to mining wastes from abandoned hard rock and uranium mines must also be considered. Experimental and epidemiologic studies have linked exposure to mining wastes that contaminate western watersheds (containing highly toxic metal mixtures of arsenic, uranium, cadmium, and other metals) to increased cancer risk in Tribal and non-Tribal communities (Environ Health Perspect. 2014;122(4):363; Cancer Epidemiol Biomark Prev. 2013;22(11):1944.).A virtually unexplored factor which may also contribute to cancer health disparities in AI/AN communities is whether the cancers that arise in American Indians have a distinct spectrum of somatic and germline genomic mutations (somatic and germline) resulting from these factors. Unfortunately, AI/AN cancer patients have been strikingly understudied to date, accounting for &lt; 0.5% of all patients studied in national cancer genomic initiatives. Cancer genomic studies previously conducted by our team of investigators in the NCI TARGET Project (https://ocg.cancer.gov &gt; programs &gt; target) focused on high-risk acute lymphoblastic leukemia (ALL) discovered that patients with a high degree of indigenous genetic ancestry had a unique spectrum of mutations in genes encoding tyrosine kinases or genes regulating tyrosine kinase pathways. All patients with this mutation spectrum had a significantly poorer overall outcome, despite treatment with intensive therapies. Recent studies have found a unique spectrum and frequency of mutations and mutational signatures in kidney cancers arising in indigenous communities (Trent, J. et al; unpublished). Our NCI-funded Participant Engagement-Cancer Genome Sequencing (PE-CGS) Research Center (NCI U2C CA252973: Engagement of American Indians of Southwestern Tribal Nations in Cancer Genomic Sequencing; MPIs: Willman and Jeffrey Trent, PhD) is seeking to overcome this knowledge gap through direct participant engagement and collaborative research partnerships with Tribal nations and communities.
A proper framework for engagement of indigenous Tribal Nations and tribal participants in research includes respect for Tribal sovereignty; engagement of participants and communities in project selection and oversight; assuring that the research is beneficent; the use of culturally-appropriate approaches for informed consent; appropriate data sharing, assurance of data privacy, and data interpretation and communication, including the need to engage AI/AN participants and communities in the development of culturally appropriate interpretive data narratives; sensitivities regarding collection and approval for use of biospecimens, particularly future use; concerns over genetic privacy, protection of individual identity, and assurance that molecular means of ancestry determination in individual Tribal members will not interfere with Tribal means of cultural identify and their Tribal membership; and joint sharing in intellectual property and the benefits of discoveries. It is our hypothesis that through appropriate participant and community engagement and comprehensive genomic sequencing, we will discover novel somatic and germline mutations, differences in the spectrum and/or frequency of cancer-promoting mutations, and genome-wide mutational signatures reflective of behaviors and exposures, that can ultimately be translated to improved cancer screening, precision prevention, and therapeutic intervention in American Indian participants and communities.
Citation Format: Cheryl L. Willman. A framework for community-engaged participatory research in cancer genomic sequencing: A collaborative with sovereign tribal nations in the American southwest [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr PL03-05.