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Leveraging Prospective Cancer Epidemiology Cohorts and Novel Methods to Improve Polygenic Risk Scores

Award Number: U01CA261339
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/28/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Leveraging Prospective Cancer Epidemiology Cohorts and Novel Methods to Improve Polygenic Risk Scores - Abstract There are stark differences in the burden of certain cancers across populations. For example, in comparison to individuals of European ancestry, African American men have a ~67% higher incidence rate of prostate cancer and Asian/Pacific Islander men and women have a 70% and 95% higher incidence rate of liver cancer, respectively. These differences in the burden of cancer across groups have been attributed to an interplay of genetic, environmental, and social factors. The inadequate representation of individuals from all ancestries limits the translational potential of GWAS findings to the world’s populations. Applying PRS developed in European ancestry individuals to other populations may result in biased risk prediction, and further exacerbate disease differences due to inaccurate assessment of individuals at high risk of disease. Here, we propose to address the drastic need for appropriate PRS construction and evaluation across multiple populations by applying new PRS approaches to the following six large-scale, longstanding cohorts: the Multiethnic Cohort (MEC); the Kaiser Resource for Genetic Epidemiology Research on Aging (GERA) cohort; the Women’s Health Initiative (WHI); the Harvard Nurses Health Studies (NHS); the Harvard Health Professionals Follow-Up Study (HPFS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Together, these cohorts include over 300,000 individuals (100,000 non-Europeans) and 91,000 incident cancer cases (24,000 non-Europeans). The individuals in these cohorts are from different ancestries. While focusing on cancer outcomes, we will utilize these unique and extensive resources to develop methods to construct and evaluate PRS, and importantly for translation, estimate absolute and excess relative risk of cancer jointly for PRS and established risk factors in multiple populations. To facilitate access to developed pipelines and data resources, we will follow F.A.I.R. analytic principles while participating with the Coordinating Center and other study sites. Ultimately, constructing and evaluating risk models in multiple populations is essential to broaden the impact of genomic medicine on human health.


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 = $300,000 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Cancer Cause and Prevention Research	002	5	8/27/2026	SUPPLEMENT FOR EXPANSION	$300,000
2026	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	5	12/22/2025	NON-COMPETING CONTINUATION	$0
2026	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	5	4/30/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $300,000

Issue Date FY: 2025 ( Subtotal = $1,000,000 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	5	8/18/2025	NON-COMPETING CONTINUATION	$1,000,000
2025	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	4	4/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,000,000

Issue Date FY: 2024 ( Subtotal = $950,000 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	4	7/2/2024	NON-COMPETING CONTINUATION	$950,000
														Subtotal = $950,000

Issue Date FY: 2023 ( Subtotal = $979,999 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	3	8/15/2023	NON-COMPETING CONTINUATION	$979,999
2023	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	2	3/20/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $979,999

Issue Date FY: 2022 ( Subtotal = $979,999 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	2	5/26/2022	NON-COMPETING CONTINUATION	$979,999
														Subtotal = $979,999

Issue Date FY: 2021 ( Subtotal = $999,722 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	1	6/16/2021	NEW	$999,722
														Subtotal = $999,722

Grand Total All Awards = $5,209,720

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Leveraging Prospective Cancer Epidemiology Cohorts and Novel Methods to Improve Polygenic Risk Scores

Award Number: U01CA261339

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 08/28/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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