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Uncovering causal protein markers to improve prostate cancer etiology understanding and risk prediction in Africans and Europeans

Award Number: R01CA263494
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men, with incidence and mortality rates varying across Africans and Europeans. The vast majority of deaths from PCa occur among the approximately 10-15% of patients diagnosed with aggressive PCa. The etiology of PCa is poorly understood. Basic research supports a crucial role of certain proteins in PCa development. Epidemiological studies also have identified multiple candidate protein biomarkers for PCa. However, conventional epidemiologic studies were conducted primarily in Europeans, and it is unclear which of the candidate protein biomarkers may be European-specific or pan-ethnic. Also, findings with many of these biomarkers have been inconsistent, potentially due to major methodological limitations, such as selection bias and uncontrolled confounding. Besides understanding etiology, identifying causal protein biomarkers can potentially contribute to improving risk prediction. For PCa, substantial efforts have been made to identify high-risk populations for improving PCa screening. However, the performance of available PCa risk prediction models remains unsatisfactory. There are critical needs to 1) apply a novel study design with reduced limitations of conventional biomarker studies for characterizing PCa causally related protein biomarkers across Africans and Europeans to improve the etiology understanding; and 2) develop improved prediction models that may effectively facilitate PCa risk/aggressiveness assessment across Africans and Europeans. One strategy to potentially decrease limitations of unmeasured confounding is to use genetic instruments for assessing the relationship between proteins and PCa. While our previous studies have utilized proteins measured in blood, it is also critical to study prostate tissue, the most relevant tissue for PCa development, as levels of many proteins show tissue-specific effects. The proposed project will apply a series of new studies to address these important knowledge gaps. Specifically, we will 1) conduct a study to identify putative causal protein biomarkers for PCa risk and aggressiveness across Africans and Europeans by applying novel methods (Aim 1); 2) functionally characterize top protein biomarkers for their roles in PCa biology (Aim 2); and 3) develop and validate ethnic-specific and pan-ethnic prediction models for PCa risk and aggressiveness, by incorporating newly identified candidate protein biomarkers and integrating results from multiple statistical methods (Aim 3). Our study will generate important new knowledge for PCa etiology, and develop improved PCa risk/aggressiveness prediction models across Africans and Europeans. The proposed new methods can also be applied to other complex diseases.


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: 2024 ( Subtotal = $656,226 )
2024	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Cause and Prevention Research	000	3	6/26/2024	NON-COMPETING CONTINUATION	$656,226
														Subtotal = $656,226

Issue Date FY: 2023 ( Subtotal = $662,482 )
2023	2023	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Cause and Prevention Research	000	2	7/31/2023	NON-COMPETING CONTINUATION	$662,482
														Subtotal = $662,482

Issue Date FY: 2022 ( Subtotal = $770,796 )
2022	2022	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Cause and Prevention Research	000	1	6/16/2022	NEW	$770,796
														Subtotal = $770,796

Grand Total All Awards = $2,089,504

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Uncovering causal protein markers to improve prostate cancer etiology understanding and risk prediction in Africans and Europeans

Award Number: R01CA263494

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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