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ALCOHOL AND BREAST CANCER

Award Number: R01AA017226
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/04/2020
PERIOD OF PERFORMANCE END DATE: 10/31/2025

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ALCOHOL AND BREAST CANCER - Epidemiological and clinical studies indicate that alcohol abuse promotes the development of breast cancer. There are two features of alcohol-induced tumor promotion: 1) alcohol consumption increases the risk of breast cancer; 2) alcohol promotes cancer progression and is associated with more aggressive forms of breast cancer. Therefore, alcohol exposure could affect both phases of mammary tumor development, namely, tumorigenesis (cell transformation and onset of tumor) and cancer aggression (tumor growth, metastasis, and drug resistance/recurrence). Adolescent alcohol drinking is a serious problem worldwide. The drinking age is getting younger while the amount of alcohol uptake per occasion has increased. Adolescent alcohol consumption is a risk factor for accidents, injuries, mental illnesses or some chronic diseases and pathologies, as well as for the appearance of addictions, including alcoholism. Although the harmful effect of adolescent alcohol exposure on the brain structures and behaviors, such as cognitive deficits and addiction has been well studied, its effect on tumor risk has never explored. The molecular mechanisms underlying alcohol tumor promotion, however, remain unclear. The adolescent is a critical period of mammary gland development. Our study indicated that adolescent mice were more sensitive to alcohol tumor promoting effect than adult mice. Our findings suggest that alcohol-induced tumorigenesis and progression/aggressiveness may operate by different mechanisms. The p21 Activated Kinases (PAKs) are a family of serine threonine kinases; PAK1 and PAK4 are particularly implicated in the carcinogenesis of mammary tumor. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38β, p38 and p38δ. Although some of their physiological functions may overlap, the role of these MAPKs is quite different. p38MAPK has been suggested to involve in the progression/aggressiveness of breast cancer. The central hypothesis for this proposal is that alcohol-promoted mammary tumorigenesis and aggressiveness is mediated by different mechanisms: alcohol-induced tumorigenesis is mainly mediated by PAK1/PDK4 and estrogen/progestrone signaling pathway in the adolescents, while alcohol-induced aggressiveness mainly is mediated by p38MAPK signaling pathway. We also hypothesize that the enhanced sensitivity of adolescent to alcohol is due to that the signaling pathways regulating the development of mammary glands are more sensitive to alcohol exposure. This proposal will test the hypothesis using both in vitro and in vivo approaches. This proposal will for the first time investigate the impact of adolescent alcohol exposure on the development of mammary glands and tumorigenesis/progression. It will not only elucidate the cellular and molecular mechanisms underlying alcohol-mediated tumor promotion, but also help to develop therapeutic strategies for treating alcohol promotion of 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: 2026 ( Subtotal = $0 )
2026	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Alcohol Research Programs	000	17	12/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $341,552 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Alcohol Research Programs	000	17	5/29/2024	NON-COMPETING CONTINUATION	$341,552
														Subtotal = $341,552

Issue Date FY: 2023 ( Subtotal = $341,552 )
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Alcohol Research Programs	000	16	4/24/2023	NON-COMPETING CONTINUATION	$341,552
														Subtotal = $341,552

Issue Date FY: 2022 ( Subtotal = $341,552 )
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Alcohol Research Programs	000	15	5/1/2022	NON-COMPETING CONTINUATION	$341,552
														Subtotal = $341,552

Issue Date FY: 2021 ( Subtotal = $341,552 )
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Alcohol Research Programs	004	14	6/1/2021	NON-COMPETING CONTINUATION	$341,552
2021	2020	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	002	12	5/17/2021	COMPETING CONTINUATION	-$10,249
2021	2020	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	000	12	4/30/2021	COMPETING CONTINUATION	-$309,246
2021	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Alcohol Research Programs	001	13	4/30/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$309,246
2021	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Alcohol Research Programs	003	13	5/17/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$10,249
														Subtotal = $341,552

Issue Date FY: 2020 ( Subtotal = $344,250 )
2020	2020	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	003	12	9/11/2020	COMPETING CONTINUATION	$10,247
2020	2020	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	000	12	5/15/2020	COMPETING CONTINUATION	$344,250
2020	2018	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	002	11	9/11/2020	SUPPLEMENT FOR EXPANSION	-$10,247
2020	2018	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	001	11	5/18/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $344,250

Issue Date FY: 2018 ( Subtotal = $411,913 )
2018	2018	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	001	11	8/23/2018	SUPPLEMENT FOR EXPANSION	$74,321
2018	2018	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	000	11	7/19/2018	NON-COMPETING CONTINUATION	$337,592
														Subtotal = $411,913

Issue Date FY: 2017 ( Subtotal = $337,592 )
2017	2017	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	000	10	8/14/2017	NON-COMPETING CONTINUATION	$337,592
														Subtotal = $337,592

Issue Date FY: 2016 ( Subtotal = $337,592 )
2016	2016	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	000	9	8/4/2016	NON-COMPETING CONTINUATION	$337,592
														Subtotal = $337,592

Issue Date FY: 2015 ( Subtotal = $327,464 )
2015	2015	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	000	8	8/5/2015	NON-COMPETING CONTINUATION	$327,464
														Subtotal = $327,464

Issue Date FY: 2014 ( Subtotal = $332,832 )
2014	2014	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	001	7	9/16/2014	COMPETING CONTINUATION	$0
2014	2014	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	000	7	9/4/2014	COMPETING CONTINUATION	$332,832
														Subtotal = $332,832

Issue Date FY: 2012 ( Subtotal = $313,667 )
2012	2012	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	109 KINEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	000	6	2/28/2012	NON-COMPETING CONTINUATION	$313,667
														Subtotal = $313,667

Issue Date FY: 2011 ( Subtotal = $313,667 )
2011	2011	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	109 KINEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	001	5	6/27/2011	NON-COMPETING CONTINUATION	$19,971
2011	2011	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	109 KINEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	000	5	2/18/2011	NON-COMPETING CONTINUATION	$293,696
														Subtotal = $313,667

Issue Date FY: 2010 ( Subtotal = $326,329 )
2010	2010	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	109 KINEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	000	4	2/18/2010	NON-COMPETING CONTINUATION	$326,329
														Subtotal = $326,329

Issue Date FY: 2009 ( Subtotal = $425,482 )
2009	2009	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	109 KINEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	004	3	3/4/2009	NON-COMPETING CONTINUATION	$296,663
2009	2009	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	109 KINEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Trans-NIH Recovery Act Research Support	006	3	7/14/2009	SUPPLEMENT FOR EXPANSION	$95,857
2009	2009	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	109 KINEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	005	3	5/5/2009	NON-COMPETING CONTINUATION	$32,962
2009	2008	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	109 KINEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	002	2	1/15/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$227,233
2009	2008	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	109 KINEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Alcohol Research Programs	003	2	2/16/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$77,812
2009	2008	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	POB 6001, UNIV SVCS CTR #3038B	MORGANTOWN	WV	26506	MONONGALIA	USA	Alcohol Research Programs	001	1	2/16/2009	NEW	$77,812
2009	2008	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	POB 6001, UNIV SVCS CTR #3038B	MORGANTOWN	WV	26506	MONONGALIA	USA	Alcohol Research Programs	000	1	1/15/2009	NEW	-$227,233
														Subtotal = $425,482

Issue Date FY: 2008 ( Subtotal = $329,625 )
2008	2008	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	POB 6001, UNIV SVCS CTR #3038B	MORGANTOWN	WV	26506	MONONGALIA	USA	Alcohol Research Programs	000	1	3/5/2008	NEW	$329,625
														Subtotal = $329,625

Grand Total All Awards = $5,166,621

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ALCOHOL AND BREAST CANCER

Award Number: R01AA017226

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/04/2020

PERIOD OF PERFORMANCE END DATE: 10/31/2025

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