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Common biology underlying pleiotropic breast, prostate and ovarian cancer risk loci

Award Number: R01CA259058
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Common biology underlying pleiotropic breast, prostate and ovarian cancer risk loci - ABSTRACT A fundamental goal of human genetics is to decipher the relationship between genotype and phenotype. Genome-wide association studies (GWAS) have identified thousands of common variants associated with numerous traits and diseases; but for the vast majority of genetic associations the underlying functional mechanisms are unknown. The key challenges in elucidating the biology underlying GWAS risk loci are: (i) to identify the susceptibility gene(s) at risk loci and their functional role in disease pathogenesis; (ii) to identify the causal risk variant(s) initiating disease development; and (iii) to establish the regulatory mechanisms by which risk variant(s) affect target gene expression An emerging feature of common variant risk loci is pleiotropy, where a risk locus shows evidence of susceptibility to two or more phenotypes. Breast, prostate and ovarian cancers share common etiologies. GWAS have so far identified more than 400 confirmed risk loci for these cancers. We have performed a meta- analysis of breast, prostate and ovarian cancers identifying more than 100 novel pleiotropic risk regions that suggest these cancers have a shared genetic component and similar underlying biology. Substantially larger genotyping studies continue to be performed in the human population and for these cancers which will provide the opportunity to identify additional breast, prostate and ovarian cancer pleiotropic risk loci. Our groups have also developed functional assays, including chromosome conformation capture, CRISPR/Cas9 genome editing, and experimental models of breast, prostate and ovarian cancer that enables us to establish the underlying biology driving neoplastic development at these risk loci in these cancer types. The overarching goals of this study are to identify shared genetic susceptibility alleles for breast, prostate and ovarian (BPO) cancers driven by non-coding DNA variation, and to establish the shared functional mechanisms that underlie disease risk for these cancers. The specific aims are: (1) To identify the credible causal risk variants, regulatory targets and candidate genes at pleiotropic BPO risk loci; (2) To utilize functional screening assays to prioritize causal risk variants, regulatory targets, and candidate genes at BPO risk loci; (3) To determine causality for risk variants, candidate genes and regulatory elements at BPO risk loci.


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: 2025 ( Subtotal = $0 )
2025	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Cause and Prevention Research	002	3	2/12/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$739,313
2025	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	2	2/12/2025	NON-COMPETING CONTINUATION	-$622,687
2025	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	1	2/12/2025	NEW	-$116,626
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $599,202 )
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Cause and Prevention Research	001	3	9/4/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$599,202
2024	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	2	9/4/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $599,202

Issue Date FY: 2023 ( Subtotal = $622,687 )
2023	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	2	9/1/2023	NON-COMPETING CONTINUATION	$622,687
														Subtotal = $622,687

Issue Date FY: 2022 ( Subtotal = $668,422 )
2022	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	1	8/16/2022	NEW	$668,422
														Subtotal = $668,422

Grand Total All Awards = $1,890,311

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Common biology underlying pleiotropic breast, prostate and ovarian cancer risk loci

Award Number: R01CA259058

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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