Polyunsaturated fatty acids and colorectal tumor risk: a molecular and genetic epidemiology study
多不饱和脂肪酸与结直肠肿瘤风险:分子和遗传流行病学研究
基本信息
- 批准号:10560524
- 负责人:
- 金额:$ 3.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-02-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:11q126p24AddressAffectAlgorithmsAnimalsAnti-Inflammatory AgentsArachidonic AcidsAreaAspirinAwardBindingBiological MarkersBloodBlood specimenCaucasiansColorectalColorectal AdenomaColorectal CancerColorectal NeoplasmsColorectal PolypComputerized Medical RecordCoxibsDNADataDiagnosisDinoprostoneDrug usageEicosanoid ProductionEicosanoidsEnzymesErythrocytesEtiologyFish OilsGeneticGenomeGenotypeGoalsIn VitroIndividualInflammatoryIntakeK-Series Research Career ProgramsKnowledgeMalignant NeoplasmsMapsMeasuresMediationMediatorMendelian randomizationMetabolismMolecular EpidemiologyMolecular Epidemiology of CancerNon-Steroidal Anti-Inflammatory AgentsObservational StudyObservational epidemiologyOmega-3 Fatty AcidsOmega-6 Fatty AcidsPIK3CA genePathway interactionsPatientsPharmaceutical PreparationsPhenotypePlasmaPolyunsaturated Fatty AcidsPrevention strategyProductionProstaglandin InhibitionProstaglandin ProductionResearchResearch TrainingResourcesRiskRisk ReductionStratificationStructural ModelsStudy SubjectSupplementationTennesseeTissue SampleTrainingTumor MarkersTumor TissueUnited StatesUniversitiesVariantWFDC2 geneadenomabiobankcancer riskcarcinogenesiscolorectal cancer preventioncolorectal cancer riskcost efficientcyclooxygenase 2dietaryepidemiology studyfatty acid metabolismgenetic epidemiologygenetic variantgenome wide association studyimprovedinflammatory markerinnovationinstrumentmodifiable risknutritionpolygenic risk scoreprogramstumorurinary
项目摘要
PROJECT SUMMARY/ABSTRACT
Arachidonic acid, a long-chain ω-6 polyunsaturated fatty acid (PUFA), has been demonstrated to affect
carcinogenesis in animal and in vitro studies. The effect of arachidonic acid is believed to be largely due to
overproduction of the eicosanoid, prostaglandin E2 (PGE2). The other class of PUFAs, ω-3, also bind to the
same enzymes involved in arachidonic acid metabolism; however, the resulting set of eicosanoids are anti-
inflammatory. Thus, ω-3 PUFA metabolism could indirectly inhibit PGE2 production and reduce cancer risk.
Over the past few years, multiple genetic variants have been identified to be associated with PUFAs. The goal
of the proposed K99/R00 award is to elucidate the potential causal association between long-chain PUFAs and
colorectal tumor risk using Mendelian randomization (MR), an approach that may avoid potential pitfalls of
conventional observational epidemiologic research. Using fine-mapping, the proposed study will identify
additional variants in key loci (11q12.2 and 6p24.2) that are involved in the conversion from short- to long-
chain PUFAs to improve the PUFA genetic instruments. The proposed study will utilize individual-level data
from the ColoRectal Transdisciplinary Study (CORECT) consortium; blood and tissue samples from the
Tennessee Colorectal Polyp Study (TCPS); and genotype and phenotype information from Vanderbilt
University's de-identified electronic medical record DNA bio-repository (BioVU). Specifically, we propose the
following aims: (1) to conduct a MR study for the association between long-chain PUFAs and colorectal cancer
risk; (2) to conduct fine-mapping to identify additional variants in key PUFA metabolism loci to improve the
genetic instruments for MR; (3) to evaluate potential interactions of genetically predicted long-chain PUFAs
(using the improved genetic instrument) and use of aspirin and non-steroidal anti-inflammatory drugs (NSAID)
with the risk of colorectal tumors; (4) to investigate associations between genetically predicted long-chain
PUFAs and selected tumor biomarkers; and (5) to conduct a mediation analysis to determine whether PGE2 is
a mediator on the causal pathway between long-chain PUFAs and colorectal adenoma risk. This innovative
study will be the first to develop an instrumental variable using a polygenic risk score in order to identify
potential causal association between long-chain PUFAs and colorectal cancer tumor risk, and will be cost-
efficient. The proposed study will help elucidate associations between long-chain PUFAs and colorectal
tumors, which could lead to potential risk reduction strategies. Lastly, the proposed career development award
will equip the candidate with the additional didactic and research training necessary for building an
independent research program in the areas of nutrition, genetics and molecular epidemiology, and cancer.
项目总结/文摘
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Using Mendelian randomisation to identify opportunities for type 2 diabetes prevention by repurposing medications used for lipid management.
- DOI:10.1016/j.ebiom.2022.104038
- 发表时间:2022-06
- 期刊:
- 影响因子:11.1
- 作者:Khankari, Nikhil K.;Keaton, Jacob M.;Walker, Venexia M.;Lee, Kyung Min;Shuey, Megan M.;Clarke, Shoa L.;Heberer, Kent R.;Miller, Donald R.;Reaven, Peter D.;Lynch, Julie A.;Vujkovic, Marijana;Edwards, Todd L.
- 通讯作者:Edwards, Todd L.
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Nikhil Kishor Khankari其他文献
Nikhil Kishor Khankari的其他文献
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{{ truncateString('Nikhil Kishor Khankari', 18)}}的其他基金
Polyunsaturated fatty acids and colorectal tumor risk: a molecular and genetic epidemiology study
多不饱和脂肪酸与结直肠肿瘤风险:分子和遗传流行病学研究
- 批准号:
10304319 - 财政年份:2021
- 资助金额:
$ 3.5万 - 项目类别:
Polyunsaturated fatty acids and colorectal tumor risk: a molecular and genetic epidemiology study
多不饱和脂肪酸与结直肠肿瘤风险:分子和遗传流行病学研究
- 批准号:
10338200 - 财政年份:2021
- 资助金额:
$ 3.5万 - 项目类别:
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