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Biological implications of breast cancer protective variants in Latin Americanwomen with high Indigenous American ancestry

Award Number: R01CA204797
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2016
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Biological implications of breast cancer protective variants in Latin Americanwomen with high Indigenous American ancestry - DESCRIPTION (provided by applicant): Breast cancer affects 1 in 8 women in the U.S. and is responsible for more than 40,000 deaths per year. Breast cancer risk is not homogeneously distributed among U.S. populations and factors responsible for differences in incidence are not yet understood. Breast cancer incidence in Latinas is 33% lower than in Non- Latina White women. We recently discovered a genetic variant that is only present in populations with Indigenous American ancestry (i.e., genetic ancestry from one of the original groups that populated the American continent before colonization), which provides protection from breast cancer risk. This polymorphism is located near the estrogen receptor 1 gene (ESR1) on chromosome 6, which has been repeatedly implicated in breast cancer. We have conducted preliminary experimental analyses that support the possibility that the genetic variant might be functional. We hypothesize that it influences ESR1 gene expression as well as expression of other genes that depend on the estrogen receptor for transcription. To test this hypothesis, we have established collaboration with the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru, where investigators have created a large repository of biospecimens, clinical data, tumor histology, treatment, and progression information. We will select biospecimens (formalin fixed paraffin embedded tumor blocks and blood samples) from 2,000 Peruvian women. There are no comparable resources available in the U.S. to study this polymorphism, which is much more common in Peru given the high average Indigenous American ancestry of this population (~80%). In Aim 1 we will examine the association between the Indigenous American genetic variant and tumor subtype, to confirm our original finding of a stronger association with tumors that are negative for the estrogen receptor, and further evaluate the subtype-specific effect, beyond just estrogen receptor characterization. In Aim 2 we will test the association between the variant and expression of the ESR1 gene, as well as expression of other genes that depend on estrogen for expression. In Aim 3, we will test the association between the genetic variant and expression of different versions of ESR1, since we hypothesize that the protective effect of the Indigenous American variant for ER negative disease could be acting through this mechanism. At the conclusion of these studies, we will have expanded our understanding of the mechanisms through which the Indigenous American variant reduces the risk of developing breast cancer and, in particular, the risk of the most aggressive and difficult to treat form of th disease. This project will provide the fundamental knowledge for the design of in-vitro and animal model experiments that could ultimately lead to the development of breast cancer preventive treatment for all women.


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 = -$3,972 )
2026	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	000	5	10/1/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$3,972
														Subtotal = -$3,972

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	000	5	9/16/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	000	5	7/10/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	000	5	7/22/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	001	5	3/17/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$83,305
2021	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	000	4	3/17/2021	NON-COMPETING CONTINUATION	-$83,305
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $507,765 )
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	001	5	8/26/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$359,138
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	002	5	8/27/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$148,627
2020	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	000	4	8/26/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $507,765

Issue Date FY: 2019 ( Subtotal = $351,691 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	000	4	8/16/2019	NON-COMPETING CONTINUATION	$351,691
														Subtotal = $351,691

Issue Date FY: 2018 ( Subtotal = $362,569 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	000	3	8/22/2018	NON-COMPETING CONTINUATION	$362,569
														Subtotal = $362,569

Issue Date FY: 2017 ( Subtotal = $362,569 )
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Biology Research	000	2	8/29/2017	NON-COMPETING CONTINUATION	$362,569
														Subtotal = $362,569

Issue Date FY: 2016 ( Subtotal = $362,569 )
2016	2016	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	000	1	3/21/2016	NEW	$362,569
														Subtotal = $362,569

Grand Total All Awards = $1,943,191

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Biological implications of breast cancer protective variants in Latin Americanwomen with high Indigenous American ancestry

Award Number: R01CA204797

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2016

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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