DNA Methylation Markers, Genes and Breast Cancer Risk
DNA 甲基化标记、基因和乳腺癌风险
基本信息
- 批准号:10378643
- 负责人:
- 金额:$ 63.97万
- 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:2021-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:ABCC1 geneAfricanAfrican ancestryAsiaAsianBioinformaticsBiologicalBiological AssayBiological ProcessBreastBreast Cancer GeneticsBreast Cancer PreventionBreast Cancer Risk FactorBreast Cancer cell lineBreast Cancer geneBreast Epithelial CellsCancer BiologyCell physiologyClustered Regularly Interspaced Short Palindromic RepeatsDNA MethylationDataDevelopmentDiagnosticDisease susceptibilityERBB2 geneEpigenetic ProcessEstrogen ReceptorsEuropeanFreezingGene ExpressionGenesGeneticGenetic DiseasesGenetic ModelsGenetic TranslationGenetic studyGenomicsGenotypeGoalsIn VitroMalignant NeoplasmsMammary Gland ParenchymaMethylationModelingModificationParticipantPathogenesisPathway interactionsPilot ProjectsPlayPositioning AttributePreventionRaceRegulationResearchResourcesRisk AssessmentRoleSamplingSeriesSiteSusceptibility GeneSystemTestingTissue BanksTissue SampleTissuesTranslatingVariantWomanYangbasecarcinogenesiscausal variantcostcost efficientdensitydisorder preventionepigenetic regulationexperienceexperimental studyfunctional genomicsgenetic variantgenome wide association studygenome wide methylationgenomic datagenomic locusimprovedinnovationinstrumentmalignant breast neoplasmmethylation biomarkermethylation patternmethylomemulti-racialmultiple omicsnovelpredictive modelingrisk stratificationtranscriptometranscriptomics
项目摘要
PROJECT SUMMARY
Genome-wide association studies (GWAS) have identified common variants in ~200 genetic loci associated
with breast cancer risk. However, it is difficult to translate these findings to disease prevention and treatment
because causal genes and underlying mechanisms in these loci are largely unknown. Increasing evidence
suggests that epigenetic regulation may be on the causal pathway between genetic variants and diseases.
DNA methylation, one of the most frequent and important epigenetic modifications, plays a crucial role in
cancer development. However, it is almost impossible to collect pre-diagnostic breast tissues to profile the
methylome from a large number of participants. Herein, we propose a novel -omics approach: a methylation-
wide association study (MeWAS) using genetic instruments. In Aim 1, we will build race-specific prediction
models using genome wide methylation and genetic data in fresh-frozen breast samples from 600 cancer-free
women of African-, Asian- and European- ancestry (200 per race). These models will then be applied to the
GWAS data from three large consortia, including ~123,000 cases and ~106,000 controls of European, ~25,000
cases and ~25,000 controls of Asian-, ~20,000 cases and ~20,000 controls of African- ancestry to impute
methylation levels. The genetically predicted methylation levels will be tested in association with breast cancer
overall and by estrogen receptor and HER2 status. In Aim 2, we will perform a series of integrative functional
analyses to evaluate the functions of promising methylation sites and the potential target genes regulated by
these methylation sites. In Aim 3, we will select the top 20 methylation sites and their target genes for in vitro
functional assays to assess their influence on major cell functions related to cancer biology. Given the strong
pilot data, unique resources from three large genetic consortia, and our team's extensive expertise and
experience, we are uniquely positioned to conduct this project. The findings will greatly improve our
understanding of the genetic and biological basis of breast cancer pathogenesis and facilitate the translation of
genetic findings to prevention and treatment.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jirong Long其他文献
Jirong Long的其他文献
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{{ truncateString('Jirong Long', 18)}}的其他基金
DNA Methylation Markers, Genes and Breast Cancer Risk
DNA 甲基化标记、基因和乳腺癌风险
- 批准号:
10623879 - 财政年份:2022
- 资助金额:
$ 63.97万 - 项目类别:
DNA Methylation Markers, Genes and Breast Cancer Risk
DNA 甲基化标记、基因和乳腺癌风险
- 批准号:
10590610 - 财政年份:2021
- 资助金额:
$ 63.97万 - 项目类别:
DNA Methylation Markers, Genes and Breast Cancer Risk
DNA 甲基化标记、基因和乳腺癌风险
- 批准号:
10220579 - 财政年份:2021
- 资助金额:
$ 63.97万 - 项目类别:
Integrating genomic and transcriptomic data to identify breast cancer susceptibility genes
整合基因组和转录组数据来识别乳腺癌易感基因
- 批准号:
10197851 - 财政年份:2019
- 资助金额:
$ 63.97万 - 项目类别:
Integrating genomic and transcriptomic data to identify breast cancer susceptibility genes
整合基因组和转录组数据来识别乳腺癌易感基因
- 批准号:
10440254 - 财政年份:2019
- 资助金额:
$ 63.97万 - 项目类别:
Integrating genomic and transcriptomic data to identify breast cancer susceptibility genes
整合基因组和转录组数据来识别乳腺癌易感基因
- 批准号:
10650297 - 财政年份:2019
- 资助金额:
$ 63.97万 - 项目类别:
Searching for new risk variants in known breast cancer risk loci in Asians
在亚洲人已知的乳腺癌风险位点中寻找新的风险变异
- 批准号:
9248748 - 财政年份:2016
- 资助金额:
$ 63.97万 - 项目类别:
Searching for new risk variants in known breast cancer risk loci in Asians
在亚洲人已知的乳腺癌风险位点中寻找新的风险变异
- 批准号:
8638596 - 财政年份:2014
- 资助金额:
$ 63.97万 - 项目类别:
Colorectal cancer risk loci: GWAS, fine-mapping, and functional analysis
结直肠癌风险位点:GWAS、精细定位和功能分析
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9248726 - 财政年份:2014
- 资助金额:
$ 63.97万 - 项目类别:
Colorectal cancer risk loci: GWAS, fine-mapping, and functional analysis
结直肠癌风险位点:GWAS、精细定位和功能分析
- 批准号:
8764139 - 财政年份:2014
- 资助金额:
$ 63.97万 - 项目类别:
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