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Identifying unique biological factors as potential targets to mitigate colorectal cancer health disparities in Native Hawaiians

Award Number: K99MD019294
ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/27/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Identifying unique biological factors as potential targets to mitigate colorectal cancer health disparities in Native Hawaiians - Project Summary / Abstract Native Hawaiians are one of the fastest growing ethnic minorities in the US, and exhibit increased incidence and mortality rates of colorectal cancer. To address these disparities, it is crucial to identify ethnic-specific genetic variations among Native Hawaiians that could offer valuable insights into colorectal cancer susceptibility and potential targets for intervention. By gaining a deeper understanding of these genetic differences, we aim to improve health outcomes and positively impact the overall well-being of Native Hawaiians. We initiated an investigation to determine if Native Hawaiian colorectal cancer possesses distinct biological variations by utilizing transcriptome sequencing (RNA-seq) analysis. Our findings revealed a set of differentially expressed genes and somatic mutations that were significantly associated with Native Hawaiian colorectal cancer. To validate the top mutated candidate genes predicted by RNA-seq, we performed whole genome DNA sequencing analysis, and unveiled some previously unrecognized somatic mutations and oncogenic signaling pathway. Therefore, we hypothesize that biologic variations unique in Native Hawaiian colorectal cancer drive aggressive tumor development, and lead to higher mortality of colorectal cancer. To test this hypothesis, we will utilize pre-existing biospecimens and comprehensive epidemiology data available from participants in the Multiethnic Cohort (U01CA164973) to identify the key risk factors contributing to colorectal cancer development among Native Hawaiians. The project outlines three specific aims that building on the preliminary studies: Aim 1: Utilize whole exome DNA sequencing to validate preliminary findings and identify more specific genetic mutations present in colorectal cancers among Native Hawaiians; Aim 2: Profile and establish unique metabolomic features specific to Native Hawaiians with colorectal cancer; Aim 3: Validate the ethnic-specific genetic and metabolomic features associated with Native Hawaiian colorectal cancer risk and clinical outcomes by independent cohort validation, while also comparing the findings with other ethnic cohorts. In completing these aims, a robust population-specific model will be developed, integrating both genetic and non-genetic factors, to identify high-risk Native Hawaiians who would benefit from screening and early intervention measures. By combining genetic, metabolomic, clinicopathologic, and epidemiologic information, this will be the first comprehensive study to examine exome-wide DNA, transcriptomic, and metabolomic profiles in colorectal tumor tissue from Native Hawaiians. In doing so, we will establish a unique resource and provide a more complete understanding of Native Hawaiian-colorectal cancer disease etiology and risk factors, which has the potential to help eliminate Native Hawaiian colorectal cancer health disparities.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $166,103 )
2025	2025	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	004	2	7/9/2025	NON-COMPETING CONTINUATION	$166,103
2025	2025	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	006	2	8/4/2025	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	005	1	8/4/2025	NEW	$0
2025	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	002	1	4/29/2025	NEW	$0
2025	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	001	1	2/19/2025	NEW	$0
2025	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	007	1	8/20/2025	NEW	$0
2025	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	003	1	6/30/2025	NEW	$0
2025	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	000	1	12/10/2024	NEW	$0
														Subtotal = $166,103

Issue Date FY: 2024 ( Subtotal = $166,103 )
2024	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	000	1	6/27/2024	NEW	$166,103
														Subtotal = $166,103

Grand Total All Awards = $332,206

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Identifying unique biological factors as potential targets to mitigate colorectal cancer health disparities in Native Hawaiians

Award Number: K99MD019294

ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/27/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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