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Methylomic basis of survival disparities among Black and White women with high-grade serous ovarian cancer

Award Number: R01CA275974
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Methylomic basis of survival disparities among Black and White women with high-grade serous ovarian cancer - Epithelial ovarian cancer is the deadliest gynecologic malignancy among women, with less than half of women surviving five years after diagnosis. Black women with ovarian cancer have worse survival compared to White women. The causes of these differences remain elusive as prior research suggests that it is not entirely due to differential access to care or guideline-adherent treatment. Thus, it remains a high priority to uncover approaches to reduce mortality and improve survival, especially for Black women. However, the majority of research on ovarian cancer is from White women, which has hindered the discovery of novel factors important for prognosis in Black women. Here, we will leverage epidemiologic, molecular, and outcome data from well-established observational studies to investigate the methylomic basis of ovarian cancer survival differences between Black and White women. DNA methylation provides a unique opportunity to investigate outcome differences as lifestyle and sociocultural conditions that are disparate between racial and ethnic groups may manifest as alterations in tumor DNA methylation, resulting in phenotypic differences between populations. We hypothesize that Black women will have a different composition of methylation patterns or a unique tumor DNA methylation signature associated with poorer survival compared to White women. To limit contributions of disease heterogeneity, we will focus on the most common and one of the deadliest histotypes, high-grade serous ovarian carcinoma (HGSOC). Among 239 Black and 478 White women with HGSOC, tumor DNA methylation will be measured using the Illumina MethylationEPIC array. Frist, data dimension reduction methods will be used to determine tumor DNA methylation signatures that are associated with survival among the overall study population and among Black and White women separately, identifying differentially methylated regions associated with outcomes that are specific to each population and those that are shared across populations. These signatures will be validated among an additional 200 Black and 200 White women with HGSOC. Second, the association between pre-diagnostic exposures that have the potential to alter DNA methylation states (e.g., age at diagnosis, smoking status) and outcome-associated DNA methylation signatures will be investigated to determine which factors may be informative for preventive strategies. As DNA methylation is highly tissue specific, the DNA methylation signature of the tumor is a weighted mixture of the methylation signature for each of the cells within the tumor. Therefore, in the third aim, we will infer cell composition from tumor DNA methylation data using a novel cell mixture deconvolution method, and examine whether inferred cell composition is associated with risk of mortality. Comparing DNA methylation across populations has important applications as this work will advance the discovery of molecular targets, aiding in clinical decision-making and informing the development of personalized therapies to reduce mortality in Black women and ultimately reduce the survival gap between Black and White women with ovarian cancer.


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 = $591,443 )
2026	2026	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	000	4	2/10/2026	NON-COMPETING CONTINUATION	$591,443
														Subtotal = $591,443

Issue Date FY: 2025 ( Subtotal = $596,383 )
2025	2025	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	001	3	6/16/2025	NON-COMPETING CONTINUATION	$59,638
2025	2025	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	000	3	12/18/2024	NON-COMPETING CONTINUATION	$536,745
														Subtotal = $596,383

Issue Date FY: 2024 ( Subtotal = $623,971 )
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	001	2	4/17/2024	NON-COMPETING CONTINUATION	$32,840
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	000	2	12/20/2023	NON-COMPETING CONTINUATION	$591,131
														Subtotal = $623,971

Issue Date FY: 2023 ( Subtotal = $706,049 )
2023	2023	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	000	1	1/19/2023	NEW	$706,049
														Subtotal = $706,049

Grand Total All Awards = $2,517,846

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Methylomic basis of survival disparities among Black and White women with high-grade serous ovarian cancer

Award Number: R01CA275974

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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