Engagement of American Indians of Southwestern Tribal Nations in Cancer Genome Sequencing

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Engagement of American Indians of Southwestern Tribal Nations in Cancer Genome Sequencing

Disparities cancers (gastrointestinal, hepatobiliary, genitourinary, and hormone dependent)
American Indians of Southwestern Tribal Nations
University of New Mexico | Mayo Clinic | Translational Genomics Research Institute (TGen) | Black Hills Center for American Indian Health
Grant Number: U2C CA252973

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Engagement of American Indians of Southwestern Tribal Nations in Cancer Genome Sequencing.

University of New Mexico | Mayo Clinic | Translational Genomics Research Institute (TGen) | Black Hills Center for American Indian Health

There is a critical underrepresentation of cancers from American Indian patients in national cancer genome databases. Additionally, American Indians have the poorest cancer survival rates of all ethnicities in the United States. The goal of this proposal is to engage with American Indian communities and individuals in order to increase their understanding and participation in precision medicine, molecular characterization of tumors and cancer research with the long-term goal of reducing their cancer burden.

While the 524 American Indian and Alaska Native (AI/AN) Tribal Nations and communities across the United States vary in ethnicity, language, and culture, there is one unfortunate characteristic they share: tremendous cancer health disparities. AI/AN are more often diagnosed at later stages of disease and have the poorest outcomes in all types of cancer, including common cancers, when compared to any other racial and ethnic group in the United States. The multilevel contextual factors underlying these disparities include significantly lower rates of cancer screening, different risk-promoting and risk-protective behaviors, significant environmental exposures resulting in part from a legacy of hard rock mining near tribal lands, and more limited access to health care. Virtually unexplored is whether AI/AN have unique or differing spectra of cancer-promoting mutations when compared to other racial/ethnic groups: only 0.25% of tumors sequenced in national genomic initiatives were identified as AI/AN. Thus, the overall purpose and goal of this PE-CGS Center is that through culturally appropriate bi-directional participant and tribal community engagement - respectful of Tribal Sovereignty, cultural practices, and beliefs - and through comprehensive clinical grade cancer genomic sequencing that is of direct beneficence to cancer patients, we will discover novel somatic and germline mutations and/or differences in the spectrum and frequency of cancer-promoting mutations, and genome-wide mutational signatures reflective of behaviors and exposures, that can be translated to improved cancer screening, precision prevention, and therapeutic intervention in tribal communities.

Project Aims

In collaboration and with the guidance of a formal Tribal Advisory Council, engage participants and indigenous tribal communities to guide all aspects of the study (approaches for engagement, consents, biospecimen use, assurance of genetic privacy, data sharing, and data interpretation and communication).
Engage and consent 800-1000 AI cancer patients from Southwestern Tribal Nations in clinical (newly diagnosed or active cancer patients) and community settings (survivors), using culturally appropriate consents reviewed by Tribal IRBs which incorporate indigenous languages and tribal art.
Consent AI patients with all forms of cancer, with a focus on cancers with significant incidence and outcome disparities in SW Tribal Nations (Pancreatic/Hepatobiliary, Colorectal, Kidney, Bladder, Breast); a statistically designed matched cohort of SW Hispanic patients with the same disparities’ cancers will also be consented.
Collect extensive participant data: behavioral, environmental exposures (NCI PhenX), family, and medical history.
Perform clinical grade WES and RNAseq on paired tumor/normal samples with return of results directly to participants and treating physicians to be of beneficence; germline mutations will also be assessed in collaboration with Invitae.
Perform research grade WGS (10-30x) to assess mutational signatures for environmental exposures/behaviors and microbiome sequencing.
Disseminate knowledge gained to Tribal participants, Tribal Councils and communities using unique means of participant engagement and communication.
Share knowledge with the broader scientific community through the NCI Genome Data Commons and publication of scientific results in accordance and subject to NIH Data Sharing Policies and Tribal Agreements.