||5U2CCA252973-02 Interpret this number
||University Of New Mexico Health Scis Ctr
||Engagement of American Indians of Southwestern Tribal Nations in Cancer Genome Sequencing
While American Indian (AI) Tribes and communities are highly diverse in ethnicity, language, and culture, there
is one unfortunate characteristic that they share: profound cancer health disparities. Compounded by
disproportionately low rates of cancer screening and more limited access to healthcare, AI 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. The cause of these significant cancer health disparities is
undoubtedly multifactorial. However, an unexplored factor is the molecular characterization of tumors arising in
AI. American Indians and Alaska Natives (AN) have been strikingly understudied in The Cancer Genome Atlas
Project (TCGA) and account for only < 0.5% of the cancer patients studied. Of the nearly 11,000 patients
sequenced in TCGA to date, only 27 (0.25%) were identified as AI/AN. 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. In this application, we will focus on the molecular characterization of cancers
which show significant disparities in AI of the Southwest, including gastrointestinal and hepatobiliary cancers
(stomach, colorectal, pancreatic, liver, gallbladder and biliary tree); genitourinary cancers (kidney, prostate
cancer); and other hormone-dependent cancers (breast, ovarian cancers). Our Specific Aims are to develop
culturally-appropriate, respectful, and trusted means to: 1) Engage American Indian participants (cancer patients
and survivors) and their Tribal communities in participatory research studies of the molecular characterization of
cancer, particularly focusing on cancers that display striking disparities in incidence and outcome in Southwest
Tribal Nations; 2) 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 specific
behaviors and exposures, in American Indian participants, relative to other racial and ethnic populations in the
U.S. and the world; 3) Disseminate knowledge gained through these studies to Tribal participants and Tribal
Councils, leaders, stakeholders, and communities using unique means of participant engagement and novel
means of communication, such as visual arts and media, that are sensitive to cultural and religious beliefs and
practices and that acknowledge the indigenous languages and dialects, many of which lack many scientific and
medical terms for words and concepts such as cancer, gene, genomics, mutation, and DNA, and 4) (Share
knowledge with the broader scientific community through the NCI Genome Data Commons and publication of
scientific results in accordance with NIH Data Sharing Policies and Tribal Agreements.
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