Somatic Mutations and Their Etiological Determinants for Breast Cancer in African American Women
非裔美国女性乳腺癌的体细胞突变及其病因决定因素
基本信息
- 批准号:10091976
- 负责人:
- 金额:$ 131.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AdmixtureAfricanAfrican AmericanAgingBreast Cancer PreventionBreast Cancer Risk FactorBreast Cancer geneBreast FeedingCancer BiologyCancer EtiologyCharacteristicsColon CarcinomaCompanionsDNA DamageDNA Sequence AlterationDataData SetData SourcesDiseaseEnvironmental Risk FactorEpidemiologyEstrogen Receptor StatusEtiologyEuropeEuropeanFactor AnalysisFrequenciesGene MutationGenesGeneticGenetic Predisposition to DiseaseGenetic ResearchGenomicsGenotypeHeterogeneityHormonalHormonesInflammationInvestigationKnowledgeLinkLiteratureMalignant NeoplasmsMalignant neoplasm of prostateMammary Gland ParenchymaMammary NeoplasmsMotivationMutateMutationObesityOxidative StressParentsPathway interactionsPatientsPlant RootsPopulationPreventivePublic HealthPublishingReportingResearchResourcesRisk FactorsSomatic MutationTestingThe Cancer Genome AtlasUnited StatesUrsidae FamilyVariantWomanWorkaggressive breast canceranticancer researchbasebreast cancer genomicscancer genomecancer health disparitycancer heterogeneitycancer subtypescancer therapycancer typeclinically significantdata resourcedesigndriver mutationepidemiologic dataexome sequencinggene panelgenetic variantgenome-wideimmunohistochemical markersimprovedknowledge basemalignant breast neoplasmmortalityparityreproductive senescencetargeted sequencingtranscriptome sequencingtriple-negative invasive breast carcinomatumortumorigenesis
项目摘要
Project Summary/ Abstract. The breast cancer health disparity between women of African ancestry (AA) and
European ancestry (EA) remains a huge public health challenge in the US. AA women are afflicted by a high
rate of the triple-negative breast cancer (TNBC), and bear the highest mortality rate of all populations from the
disease. Even within TNBC, some data suggest AA women fare worse than EA women. Mounting evidence
points to possible population differences in cancer biology, a fundamental question that remains unsettled. The
disparity also manifests in representativeness in tumor genomic sequencing projects. The existing data of
breast tumor mutations are dominated by cases from EA populations, which may not represent AA cancer
genomes. Moreover, as discovery potential for new driver genes has come close to a plateau, cancer genomes
in AAs raised in distinct genetic and environmental context may provide a powerful venue for uncovering
mutations that are rare in EA cases. This is clearly showcased in recent studies in other cancer types. Thus,
we propose here a study to characterize the mutational landscape of AA breast cancer genomes by pooling
resources from five studies, which will create the largest AA tumor mutation dataset. We hypothesize that
endogenous and exogenous exposures leave characteristic mutational signatures on cancer genome,
providing a trackable historic record of cancer etiology and heterogeneity. Thus, we will investigate etiological
links of tumor mutations with genetic and environmental factors by leveraging the available rich epidemiologic
and genotype data resources. We have four Specific Aims. First, we will characterize mutational landscape of
TNBC in AA women by performing whole-exome sequencing and RNA-sequencing of 500 tumors. We will
identify and compare significantly mutated genes and mutational signatures in AA TNBC cases with EA cases
from public data sources, to test whether there are population-level differences. Second, based on data from
Aim 1 and published literature, we will assemble a targeted gene panel and sequence an additional 2,500 AA
tumors, inclusive of all subtypes. The design will cover all genes included in B-CAST, an ongoing breast tumor
sequencing project of EA cases in Europe. Data generated in Aim 2 will be used to validate SMGs identified in
Aim 1, and to further assess population-level mutational differences in comparison to EA data from B-CAST
and others across all cancer subtypes. Third, we will examine etiological links between hormone-related risk
factors for breast cancer and somatic mutations. Fourth, we will examine genetic ancestry and genetic variants
with tumor mutations. On the basis of the data above, we will identify breast cancer etiological subtypes using
an integrative analytical approach. The proposed work will greatly advance the field of breast cancer research
by characterizing tumor mutational landscape in AA populations and determining whether cancer biology at the
somatic mutation level differs by ancestral population. The findings may have translational significance by
revealing cancer causation and providing new targets and motivations for cancer preventive initiatives.
项目摘要/摘要。非洲裔妇女乳腺癌健康状况的差异(AA)和
项目成果
期刊论文数量(0)
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JOHN D. CARPTEN其他文献
JOHN D. CARPTEN的其他文献
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{{ truncateString('JOHN D. CARPTEN', 18)}}的其他基金
USC PE-GCS: Optimizing Engagement of Hispanic Colorectal Cancer Patients in Cancer Genomic Characterization Studies
USC PE-GCS:优化西班牙裔结直肠癌患者参与癌症基因组特征研究
- 批准号:
10492733 - 财政年份:2021
- 资助金额:
$ 131.07万 - 项目类别:
USC PE-GCS: Optimizing Engagement of Hispanic Colorectal Cancer Patients in Cancer Genomic Characterization Studies
USC PE-GCS:优化西班牙裔结直肠癌患者参与癌症基因组特征研究
- 批准号:
10696237 - 财政年份:2021
- 资助金额:
$ 131.07万 - 项目类别:
USC PE-GCS: Optimizing Engagement of Hispanic Colorectal Cancer Patients in Cancer Genomic Characterization Studies
USC PE-GCS:优化西班牙裔结直肠癌患者参与癌症基因组特征研究
- 批准号:
10294884 - 财政年份:2021
- 资助金额:
$ 131.07万 - 项目类别:
Somatic Mutations and Their Etiological Determinants for Breast Cancer in African American Women
非裔美国女性乳腺癌的体细胞突变及其病因决定因素
- 批准号:
10335127 - 财政年份:2019
- 资助金额:
$ 131.07万 - 项目类别:
Somatic Mutations and Their Etiological Determinants for Breast Cancer in African American Women
非裔美国女性乳腺癌的体细胞突变及其病因决定因素
- 批准号:
10558682 - 财政年份:2019
- 资助金额:
$ 131.07万 - 项目类别:
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