A Transdisciplinary Approach to Investigating Metabolic Dysregulation in Obese Parent and Child Dyads and Risk of Colorectal Cancer
采用跨学科方法研究肥胖父母和儿童二人组的代谢失调和结直肠癌风险
基本信息
- 批准号:10684760
- 负责人:
- 金额:$ 110.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-16 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:3 year oldAddressAdipocytesAdipose tissueAdultAfrican AmericanAfrican American populationAge YearsAmericanAnimal ExperimentsAnimalsAnti-Inflammatory AgentsAntiinflammatory EffectBacteriaBiological AssayC-reactive proteinCancer ControlCancer InterventionCancer ModelCellsChildChronicClinical TrialsColon CarcinomaColorectal CancerCommunicationComplementComplement 2ConsumptionDietDietary InterventionDisparityEnrollmentEpidemiologyEuropeanGoalsGrantHealthHigh Fat DietHumanIncidenceInflammationInflammation MediatorsInflammatoryInfluentialsInfrastructureInsulinInsulin ResistanceInsulin-Like Growth Factor IInterleukin-6InterventionIntervention TrialLaboratory AnimalsLinkLiteratureMacrophageMalignant NeoplasmsMediatorMedicalMetabolicMetabolic dysfunctionModelingObese MiceObesityObesity associated cancerOutcomePaperParentsPathogenesisPopulationPublishingRaceRiskRoleScienceSomatomedinsSouth CarolinaStudy modelsSystemTNF geneTestingUnhealthy DietUniversitiesWorkadenomaadiponectinanticancer researchassociated symptomcancer epidemiologycancer health disparitycancer preventioncarcinogenesiscolorectal cancer progressioncolorectal cancer riskcytokinedietaryearly onset colorectal cancerepidemiology studyexperienceexperimental studyfecal transplantationgut microbesgut microbiotahigh riskhuman studyin vivoinflammatory markerintestinal barrierlifestyle interventionmicrobiomemicrobiome signaturemicrobiotamouse modelobesity in childrenpre-clinicalpreventprogramsprotective effectprotective factorsracial differenceracial identityresponsesystemic inflammatory responsetumorigenesis
项目摘要
This U01 project leverages our expertise in the epidemiology of colorectal cancer (CRC); disparities; obesity;
metabolic dysregulation, an important manifestation of inflammation; the microbiome; animal CRC models; and
lifestyle intervention trials to address the growing problem of Early-Onset CRC (EOCRC) (i.e., <50 years).
Adiposity and diet drive metabolic dysregulation. So, understanding the interaction between diet and adiposity
are key to understanding the genesis of EOCRC – and an array of other obesity-related cancers). This project
will address the absence of critical clinical trials and mechanistic studies involving lifestyle interventions for
EOCRC. We intend to address this gap; and have the transdisciplinary team representing complementary
backgrounds to do so. We focus on dietary modulation of gut microbes to reduce metaflammation and
subsequent metabolic dysfunction in obesity, with a goal of preventing EOCRC. We will perform 1) an anti-
inflammatory dietary intervention trial in dyads of adults and children at elevated risk for CRC. We also will
conduct a complementary mechanistic animal study that builds on and leverages our expertise in mechanistic
studies on obesity and CRC. This work is supported by infrastructure that we have built over the past decades
in two key centers at the University of South Carolina (UofSC): (1) Center for Colon Cancer Research (CCCR,
2002 - present – which specializes in mouse models of CRC); and (2) the Cancer Prevention and Control
Program (CPCP, 2000 - present – which specializes in the epidemiology of cancer and lifestyle intervention
trials for cancer, with a focus on cancer disparities. The two projects that comprise the proposed grant address
two Specific Aims that are represented by the human study and laboratory animal experiment: i.e. ,1: To
establish the metabolic protective effects of an anti-inflammatory diet in obese, high-risk African-
American (AA) and European-American (EA) adults and children in reducing inflammation as indicated by
Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), IGF-1, Tumor Necrosis Factor alpha
(TNFα), Interleukin 6 (IL-6), and C-Reactive Protein (CRP), and a creating more favorable microbiome
signature; 2: To establish gut microbes as mediators between anti-inflammatory dietary input and
reversal of metabolic dysfunction and associated CRC risk. This complements the human study by
carrying out pre-clinical murine model studies with similar inputs (diet), intermediate endpoints (inflammation,
microbiome), and outcomes (CRC-related). We hypothesize that an anti-inflammatory dietary intervention will
reduce metabolic dysfunction and metainflammation through regulatory effects on gut microbiota.
Results from this work will address the role of metabolic dysregulation in relation to factors that are known to
be important in carcinogenesis, that therefore could have profound effects on EOCRC, have implications for
other obesity-related cancers, and have great promise for moving the field forward by addressing mechanisms
that drive large health-related disparities that consistently disfavor African Americans.
U01项目利用了我们在结直肠癌(CRC)流行病学方面的专业知识;差距;肥胖;
项目成果
期刊论文数量(0)
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JAMES R HEBERT其他文献
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{{ truncateString('JAMES R HEBERT', 18)}}的其他基金
A Transdisciplinary Approach to Investigating Metabolic Dysregulation in Obese Parent and Child Dyads and Risk of Colorectal Cancer
采用跨学科方法研究肥胖父母和儿童二人组的代谢失调和结直肠癌风险
- 批准号:
10505332 - 财政年份:2022
- 资助金额:
$ 110.47万 - 项目类别:
Expand NCI-Supported Community Outreach Capacity
扩大 NCI 支持的社区外展能力
- 批准号:
8759438 - 财政年份:2013
- 资助金额:
$ 110.47万 - 项目类别:
Research Supplements to Promote Diversity in Health-Related Program
促进健康相关项目多样性的研究补充
- 批准号:
8759457 - 财政年份:2013
- 资助金额:
$ 110.47万 - 项目类别:
South Carolina Cancer Disparities Community Network -- II
南卡罗来纳州癌症差异社区网络 -- II
- 批准号:
8911967 - 财政年份:2010
- 资助金额:
$ 110.47万 - 项目类别:
South Carolina Cancer Disparities Community Network -- II
南卡罗来纳州癌症差异社区网络 -- II
- 批准号:
8730838 - 财政年份:2010
- 资助金额:
$ 110.47万 - 项目类别:
South Carolina Cancer Disparities Community Network -- II
南卡罗来纳州癌症差异社区网络 -- II
- 批准号:
8538767 - 财政年份:2010
- 资助金额:
$ 110.47万 - 项目类别:
South Carolina Cancer Disparities Community Network -- II
南卡罗来纳州癌症差异社区网络 -- II
- 批准号:
8323608 - 财政年份:2010
- 资助金额:
$ 110.47万 - 项目类别:
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