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Early life prevention of breast cancer with combined epigenetic botanicals

Award Number: R01CA204346
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2017
PERIOD OF PERFORMANCE END DATE: 12/31/2022

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Early life prevention of breast cancer with combined epigenetic botanicals - Use of dietary botanicals for maintaining health can be greatly enhanced through elucidation of their effects on epigenetic mechanisms, their combined impact and their efficacy at different life stages, especially early in life. Epigenetic aberrations often alter key gene expressions that are crucial in maintaining health and delaying the onset and reducing the impact of cancer. However, very little is known with respect to the impact of dietary botanicals consumed in combination early in life on epigenetic mechanisms and the risk of developing cancer. Our studies have indicated that green tea polyphenols (GTPs) and sulforaphane (SFN)-rich broccoli sprouts (BSp), administered in combination at safe levels consumable by humans, are highly effective in increasing cancer latency in mice that spontaneously develop estrogen receptor (ER)-negative [ER(-)] breast cancer and that this may be more effective when administered early in life. It is important that although most ER(+) breast cancer is relatively highly responsive to therapy once it forms, ER(-) breast cancer has high mortality rates if it is not prevented from developing. Therefore, cancer prevention approaches that reduce ER(-) breast cancer will have by far the greatest impact on the incidence of cancer fatalities. Our results indicate that the efficacy of this dietary approach depends on the ability of these botanicals to significantly impact epigenetic gene regulation. Our hypothesis is that early life consumption of combined GTPs and BSp is highly effective in neutralizing epigenomic alterations and epigenetic control of key genes that lead to ER(-) BC formation and progression. These studies will be important to determine the efficacy of botanicals at various stages of life so that their consumption will optimize the potential for cancer prevention. We do not yet fully understand the epigenetic mechanisms of these botanicals consumed at different stages of life and especially in combination as they are often consumed. Further, the impact of these botanicals on global epigenomic processes at various ages is not yet known. A major goal of this proposed investigation is to confront these persistent challenges. The incorporation of these botanicals into diets of the young is safe and could lead to important revisions of dietary regimens to increase cancer latency and to significantly reduce the incidence of ER(-) breast cancer fatalities. Novel techniques such as chromatin immunoprecipitation-genomic bisulfite sequencing (ChIP-GBS) that we invented as well as several advanced epigenomic technologies will be employed. Elucidation of the epigenetic mechanisms for cancer latency and reducing the risk of cancer will result in significant increases in the health of hundreds of thousands of individuals worldwide. This investigation will also provide essential information for identification of epigenetic biomarkers of breast cancer at different stages of life that will facilitate elucidation of the predisposition, diagnosis and prognosis of breast cancer. Most importantly, the use of safe and effective epigenetic aberration-neutralizing botanicals in early life has high translational potential for increasing the latency and reducing the impact of ER(-) breast 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: 2024 ( Subtotal = $0 )
2024	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	5	10/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $334,344 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	5	12/8/2020	NON-COMPETING CONTINUATION	$317,626
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	001	5	1/21/2021	NON-COMPETING CONTINUATION	$16,718
														Subtotal = $334,344

Issue Date FY: 2020 ( Subtotal = $334,344 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	001	4	1/13/2020	NON-COMPETING CONTINUATION	$33,435
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	4	1/1/2020	NON-COMPETING CONTINUATION	$300,909
														Subtotal = $334,344

Issue Date FY: 2019 ( Subtotal = $324,313 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	3	12/21/2018	NON-COMPETING CONTINUATION	$324,313
														Subtotal = $324,313

Issue Date FY: 2018 ( Subtotal = $334,344 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	001	2	5/22/2018	NON-COMPETING CONTINUATION	$33,435
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	2	12/11/2017	NON-COMPETING CONTINUATION	$300,909
														Subtotal = $334,344

Issue Date FY: 2017 ( Subtotal = $334,344 )
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	1	12/12/2016	NEW	$334,344
														Subtotal = $334,344

Grand Total All Awards = $1,661,689

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Early life prevention of breast cancer with combined epigenetic botanicals

Award Number: R01CA204346

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2017

PERIOD OF PERFORMANCE END DATE: 12/31/2022

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