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Genomic and Genomic Variation in Prostate Cancer

Award Number: R01CA259200
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/07/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Genomic and Genomic Variation in Prostate Cancer - There is consistent evidence that germline genetics and tumor (somatic) genomics have a substantial impact on the incidence (occurrence) of prostate cancer. Prostate cancer incidence has one of the highest heritabilities of any common cancer. Over 450 low penetrance genetic variants have been identified by genome-wide association studies, and numerous high penetrance pathogenic variants are established to cause prostate cancer. In addition, there is growing evidence for substantial variation in the mutational landscape of prostate tumors. These pathways include known carcinogenesis mechanisms such as DNA damage repair, immunological surveillance, and steroid hormone metabolism. Molecularly-defined tumor subtypes are emerging that likely confer differences in prostate cancer progression and treatment response. These observations support the hypothesis that genetic and genomic factors influence prostate cancer incidence and tumor aggressiveness. Limited genetic variation to date has been available to inform the optimal clinical translation of genetic and genomic features for American men with prostate cancer. It has been demonstrated that research that does not account for the full range of genotypic or genomic variation leads to genetic misdiagnoses and other errors that result in sub-optimal clinical translation of this information. Thus, to inform the genetic and genomic basis of prostate cancer, we propose to address the following Aims: Aim 1: Identify common genetic variants associated with prostate cancer aggressiveness; Aim 2: Define histopathological features of prostate tumors that correlate with germline genetic and tumor somatic genomic variation; and Aim 3: Evaluate molecular signatures and subtypes in prostate tumors to improve clinical translation of genetic and genomic data. Our research will combine data from multiple sources to address the critical need for optimized variability in cancer genomics data. Maximal variation in genetic and genomic data will not only improve our understanding of genomic contributors to prostate cancer etiology and also aid in the development and translation of cancer genomic tools, reduce the potential for errors in determining pathogenicity of genetic susceptibility variants, and improve interpretation of cancer risk assessment for Americans. we will improve the ability to predict which American men will benefit from risk-stratified prostate cancer prevention, early detection, and precision medicine therapeutics. We have constructed these resources to integrate directly with existing publicly available databases, such as TCGA/ICGC and GENIE, to ensure our data can be readily compared with data from other sources. Our data will also include deep pathology, clinical and risk factor annotation, largely unavailable in current public datasets, to provide a fuller potential to understand of prostate cancer etiology and progression. To optimize genetic variability, we have developed a large, multicenter network known as “Men of African Descent and Carcinoma of the Prostate” (MADCaP). This network of African sites includes 37 Military Hospital (Accra, Ghana), GloCare Health Institute (Dakar, Senegal), Korle-Bu Teaching Hospital (Accra, Ghana), Mbingo Baptist Hospital (Mbingo, Cameroon), University of Abuja Teaching Hospital (Abuja, Nigeria), University Of Calabar Teaching Hospital (Calabar, Nigeria), University College Hospital (Ibadan, Nigeria), Wits Health Consortium (Johannesburg, South Africa), and Stellenbosch University (Cape Town, South Africa). This network provides germline samples from a wide range of ancestral populations to create a rich data resource of ancestral genetic variation. These samples and the resulting data include genetic variability that is not available in the US and is critical to understand the underpinnings of CaP etiology and progression in American men.


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: 2026 ( Subtotal = $980,931 )
2026	2026	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	001	5	6/26/2026	SUPPLEMENT FOR EXPANSION	$19,607
2026	2026	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	000	5	6/9/2026	NON-COMPETING CONTINUATION	$961,324
														Subtotal = $980,931

Issue Date FY: 2025 ( Subtotal = $1,298,318 )
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	002	4	8/12/2025	SUPPLEMENT FOR EXPANSION	$19,607
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	001	4	8/5/2025	NON-COMPETING CONTINUATION	$981,414
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	004	4	8/21/2025	SUPPLEMENT FOR EXPANSION	$48,417
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	006	4	8/25/2025	SUPPLEMENT FOR EXPANSION	$44,377
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	007	4	8/26/2025	SUPPLEMENT FOR EXPANSION	$56,012
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	008	4	8/27/2025	SUPPLEMENT FOR EXPANSION	$53,769
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	005	4	8/22/2025	SUPPLEMENT FOR EXPANSION	$55,368
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	003	4	8/19/2025	SUPPLEMENT FOR EXPANSION	$39,354
2025	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	000	3	8/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,298,318

Issue Date FY: 2024 ( Subtotal = $1,256,800 )
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	001	3	4/17/2024	NON-COMPETING CONTINUATION	$66,147
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	000	3	2/12/2024	NON-COMPETING CONTINUATION	$1,190,653
														Subtotal = $1,256,800

Issue Date FY: 2023 ( Subtotal = $1,284,929 )
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Cause and Prevention Research	000	2	1/27/2023	NON-COMPETING CONTINUATION	$1,284,929
														Subtotal = $1,284,929

Issue Date FY: 2022 ( Subtotal = $1,324,467 )
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Cause and Prevention Research	000	1	1/7/2022	NEW	$1,324,467
														Subtotal = $1,324,467

Grand Total All Awards = $6,145,445

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Genomic and Genomic Variation in Prostate Cancer

Award Number: R01CA259200

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/07/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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