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Latin America Genomics of Breast Cancer Risk Study (LAGENO-BCR)

Award Number: R01CA286650
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Latin America Genomics of Breast Cancer Risk Study (LAGENO-BCR) - SUMMARY/ABSTRACT Breast cancer is a leading cause of death in the U.S. and a major public health burden as one woman out of eight will receive a diagnosis in her lifetime. Advances in DNA genotyping and sequencing technologies have led to the identification of >300 germline variants that contribute to breast cancer risk. However, as of today, large ‘omics’ studies include women of mostly European ancestry even though preliminary evidence indicates that there is a clear benefit in studying genetically diverse samples. A genome wide association study (GWAS) in Hispanic/Latina (H/L) women with one tenth of the number of individuals included in previous studies led to the discovery of protective variants only present in populations that have Indigenous American ancestry. These variants significantly add to the predictive accuracy of breast cancer polygenic risk scores (PRS). H/L represent 16% of the U.S. population and in some states, up to 37%. To address the lack of H/L representation in genomics studies, we have created the Latin America genomics of breast cancer (LAGENO-BC) consortium, which includes ~28,500 Latin American breast cancer patients and ~32,600 unaffected women from 11 different countries and the U.S. diaspora. Our goal is to study the Latin American-specific genetic architecture of breast cancer and develop predictive models that account for variation by ancestry and geography. By combining existing studies, LAGENO-BC quadruples the prior H/L BC GWAS sample size and consequently, provides the power required for the discovery of additional variants contributing to breast cancer risk and for improving the predictive power of PRS for risk stratification in those populations. In the first aim, we propose to discover susceptibility loci and genes associated with breast cancer in H/Ls by conducting GWAS and ancestry-matched multi-tissue model-based transcriptome wide association studies with readily available RNA sequence data (TWASs). These analyses will be repeated for overall risk and subtype-specific risk. In the second aim, we will use known and new genetic risk variants to improve breast cancer risk prediction using ancestry-aware approaches and integrating existing models based on non-genetic risk factors. This work is expected to result in the discovery of new risk variants that are especially relevant to populations with an admixed Indigenous American ancestral background. In addition, utilizing ancestry-matched and multi-tissue models for TWAS, new associations linked to ancestry- specific and tissue-specific eQTLs are expected to be uncovered. It is also expected that PRS scores that incorporate H/Ls variants and assess regional and ancestry heterogeneity will be more predictive than a one-size-fits-all approach. Beyond the proposed work in this application, LAGENO-BC is building up a resource that will serve as a foundation for future collaborative studies addressing a broad range of scientific questions related to breast cancer genetics in H/L populations.


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 = $0 )
2026	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Cause and Prevention Research	000	2	11/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $827,974 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Cause and Prevention Research	001	2	9/17/2025	SUPPLEMENT FOR EXPANSION	$8,640
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Cause and Prevention Research	005	2	9/18/2025	SUPPLEMENT FOR EXPANSION	$11,664
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Cause and Prevention Research	000	2	9/16/2025	NON-COMPETING CONTINUATION	$730,089
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Cause and Prevention Research	002	2	9/18/2025	SUPPLEMENT FOR EXPANSION	$46,801
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Cause and Prevention Research	004	2	9/18/2025	SUPPLEMENT FOR EXPANSION	$22,140
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Cause and Prevention Research	003	2	9/18/2025	SUPPLEMENT FOR EXPANSION	$8,640
														Subtotal = $827,974

Issue Date FY: 2024 ( Subtotal = $872,878 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Cause and Prevention Research	000	1	8/29/2024	NEW	$872,878
														Subtotal = $872,878

Grand Total All Awards = $1,700,852

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Latin America Genomics of Breast Cancer Risk Study (LAGENO-BCR)

Award Number: R01CA286650

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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