Methylomic basis of survival disparities among Black and White women with high-grade serous ovarian cancer
患有高级别浆液性卵巢癌的黑人和白人女性生存差异的甲基组学基础
基本信息
- 批准号:10561082
- 负责人:
- 金额:$ 70.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-01-01 至 2027-12-31
- 项目状态:未结题
- 来源:
- 关键词:AccountingAfrican AmericanAgeB-LymphocytesBehaviorBlack raceCD8B1 geneCancer PatientCancer PrognosisCellsCessation of lifeCharacteristicsCox ModelsCytosineCytotoxic T-LymphocytesDNA MethylationDataDevelopmentDiagnosisDiagnosticDietDimensionsDisparateDisparityEconomicsEducationEndothelial CellsEpidemiologyEpithelial CellsEpithelial ovarian cancerEthnic PopulationGene ExpressionGeneticGuanine NucleotidesGuidelinesHealth Services AccessibilityImmuneLife StyleMalignant Female Reproductive System NeoplasmMalignant NeoplasmsMalignant neoplasm of ovaryMeasuresMethodsMethylationMinorityMinority GroupsModelingMolecularMolecular TargetNatural Killer CellsNorth CarolinaNurses&apos Health StudyObesityObservational StudyOutcomeOvarian Serous AdenocarcinomaPhenotypePhysical activityPopulationPopulation StudyPrevention strategyPrognosisPrognostic FactorRaceRegulator GenesRegulatory T-LymphocyteReportingResearchResourcesSerousSiteSmokingSmoking StatusStromal CellsTestingTimeTissuesUnderrepresented MinorityWeightWomanWorkbead chipblack womencancer epidemiologycancer survivalcell typeclinical decision-makingdifferences in accessdisease heterogeneitydisparity reductioneosinophilepidemiology studygenome-wideimprovedindividualized preventioninnovationmethyl groupmethylation biomarkermethylation patternmethylomicsmonocytemortalitymortality riskneutrophilnovelovarian neoplasmpersonalized medicinepreventive interventionracial determinantracial differenceracial minority populationracial populationsocialsocial culturestudy populationsurvival disparitytargeted treatmenttumortumor DNAtumor microenvironment
项目摘要
ABSTRACT
Epithelial ovarian cancer is the deadliest gynecologic malignancy among women, with less than half of women
surviving five years after diagnosis. Black women with ovarian cancer have worse survival compared to White
women. The causes of these disparities remain elusive as prior research suggests that it is not entirely due to
differential access to care or guideline-adherent treatment. Thus, it remains a high priority to uncover approaches
to reduce mortality and improve survival, especially for Black women. However, the majority of research on
ovarian cancer is from White women, which has hindered the discovery of novel factors important for prognosis
in underrepresented minority groups. Here, we will leverage epidemiologic, molecular, and outcome data from
well-established observational studies to investigate the methylomic basis of ovarian cancer survival disparities
between Black and White women. DNA methylation provides a unique opportunity to investigate disparities as
lifestyle and sociocultural conditions that are disparate between racial/ethnic groups may manifest as alterations
in tumor DNA methylation, resulting in phenotypic differences between populations. We hypothesize that Black
women will have a different composition of methylation patterns or a unique tumor DNA methylation signature
associated with poorer survival compared to White women. To limit contributions of disease heterogeneity, we
will focus on the most common and one of the deadliest histotypes, high-grade serous ovarian carcinoma
(HGSOC). Among 239 Black and 478 White women with HGSOC, tumor DNA methylation will be measured
using the Illumina MethylationEPIC array. Frist, data dimension reduction methods will be used to determine
tumor DNA methylation signatures that are associated with survival among the overall study population and
among Black and White women separately, identifying differentially methylated regions associated with
outcomes that are specific to each race and those that are shared across race. These signatures will be validated
among an additional 200 Black and 200 White women with HGSOC. Second, the association between pre-
diagnostic exposures that have the potential to alter DNA methylation states (e.g., age at diagnosis, smoking
status) and outcome-associated DNA methylation signatures will be investigated to determine which factors may
be informative for preventive strategies. As DNA methylation is highly tissue specific, the DNA methylation
signature of the tumor is a weighted mixture of the methylation signature for each of the cells within the tumor.
Therefore, in the third aim, we will infer cell composition from tumor DNA methylation data using a novel cell
mixture deconvolution method, and examine whether inferred cell composition is associated with risk of mortality.
Comparing DNA methylation across populations has important applications as this work will advance the
discovery of molecular targets among an underrepresented racial minority group, aiding in clinical decision-
making and informing the development of personalized therapies to reduce mortality in Black women and
ultimately reduce the survival gap between Black and White women with ovarian cancer.
摘要
项目成果
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Lauren Cole Peres其他文献
Lauren Cole Peres的其他文献
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{{ truncateString('Lauren Cole Peres', 18)}}的其他基金
The Role of Inflammation in the Racial Disparities in Ovarian Cancer Survival
炎症在卵巢癌生存的种族差异中的作用
- 批准号:
9977134 - 财政年份:2017
- 资助金额:
$ 70.6万 - 项目类别:
Project 2: The impact of biobehavioral factors and aspirin on ovarian cancer biology
项目2:生物行为因素和阿司匹林对卵巢癌生物学的影响
- 批准号:
10762082 - 财政年份:2012
- 资助金额:
$ 70.6万 - 项目类别:
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