Polygenic Risk Prediction of Breast Cancer for Women of African Descent
非洲裔女性乳腺癌的多基因风险预测
基本信息
- 批准号:10748724
- 负责人:
- 金额:$ 51.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-04-19 至 2028-07-01
- 项目状态:未结题
- 来源:
- 关键词:AddressAfricanAfrican AmericanAfrican American populationAfrican ancestryAgeAsianAsian ancestryAsian populationAssessment toolBreast Cancer DetectionBreast Cancer GeneticsBreast Cancer ModelBreast Cancer Risk FactorCase/Control StudiesClinicalCohort StudiesComplexDataData PoolingData SetDevelopmentElasticityEpidemiologyEstrogen ReceptorsEstrogen receptor negativeEstrogen receptor positiveEthnic PopulationEuropean ancestryFamily history ofFundingGene FrequencyGenesGeneticGenetic CounselingGenetic DiseasesIncidenceIndividualInvestigationKnowledgeLassoLeftLife StyleLinkage DisequilibriumMammographic screeningMapsMethodsModelingMutationNoiseOutcomePenetrancePerformancePopulationPredispositionPreventionPublic DomainsQuantitative Trait LociRNA SplicingRaceRacial EquityReproductive HistoryRiskRisk AssessmentRisk FactorsSample SizeScoring MethodSignal TransductionStatistical MethodsSusceptibility GeneTarget PopulationsTestingTrainingTranslatingVariantVeteransWomanaccess disparitiesancestry analysisblack womencancer subtypescausal variantclinical practicecohortearly onsetgenetic predictorsgenetic variantgenome wide association studygenome-widegenome-wide analysisgenomic locushigh riskimprovedinnovationmalignant breast neoplasmmortalitymulti-ethnicnon-geneticnovelpolygenic risk scoreprecision medicineracial disparityracial populationrisk predictionrisk prediction modelrisk stratificationrisk variantscreeningstatisticstooltranscriptometranscriptome sequencingtranscriptomicstranslational impacttriple-negative invasive breast carcinoma
项目摘要
PROJECT ABSTRACT
African Americans have the highest breast cancer mortality rate, highest incidence rate of early-onset
breast cancer, and highest incidence rate of triple-negative breast cancer in the U.S. More than 220
susceptibility loci for breast cancer have been identified by genome-wide association studies (GWAS), mainly
in population of European ancestry. Polygenic risk scores (PRS), which aggregate common genetic variants
identified by GWAS, have been developed to predict genetic risk of breast cancer for European ancestry
women and used in clinical practice, but the PRS for African American women has suboptimal accuracy.
Therefore, we propose a comprehensive analytical study that leverages several types of existing genetic
datasets for breast cancer available to us and in public domains to address three specific aims. First, we aim
to conduct cross-ancestry fine-mapping analysis to identify a credible set of causal variants in 237 breast
cancer susceptibility loci. Then we will develop parsimonious and robust PRS from the credible set of variants.
We have compiled and harmonized genetic data from breast cancer GWASs in women of African ancestry,
including 18,034 cases and 22,104 controls, and leverage the association results from European ancestry
(>133,000 cases and >291,000 controls) and Asian (>22,000 cases and >22,000 controls) populations.
Second, we aim to develop precise PRS using genome-wide data with several novel cross-ancestry statistical
methods. We will develop PRS models for overall breast cancer and its subtypes (estrogen receptor positive
and negative, and triple-negative breast cancer). Then we will validate the models generated in aims 1-2 in
independent datasets (>14,000 cases and >82,000 controls) from case-control studies, ongoing cohort studies,
and an ongoing risk-adaptive breast cancer screening trial. Third, we will integrate the best performed PRS
with existing risk prediction models that are based on non-genetic risk factors. The resulting absolute risk
models have a good potential to translate knowledge from GWAS to inform the practice of genetic counseling,
breast cancer screening and prevention for African Americans. It has good potential to advance racial equity in
breast cancer.
项目摘要
非裔美国人的乳腺癌死亡率最高,早发病率最高
在美国,乳腺癌和三阴性乳腺癌的发病率最高220
乳腺癌的易感基因座已通过全基因组关联研究(GWAS)确定,主要是
在欧洲血统的人口中。多基因风险评分(PRS),汇总常见遗传变异
由GWAS确定,已开发出来预测欧洲血统的乳腺癌遗传风险
妇女并用于临床实践,但非裔美国妇女的PR具有不错的准确性。
因此,我们提出了一项全面的分析研究,利用几种类型的现有遗传
乳腺癌数据集可用于我们和公共领域,以解决三个特定目标。首先,我们的目标
进行跨委托的精细映射分析以识别237乳中的一组可信因果变体
癌症敏感性基因座。然后,我们将从可信的变体集中发展出简约而强大的PR。
我们已经在非洲血统的妇女中汇编并协调了乳腺癌Gwass的遗传数据,
包括18,034例案件和22,104个对照,并利用欧洲血统的协会结果
(> 133,000例和> 291,000个对照)和亚洲(> 22,000例和> 22,000个对照)人群。
其次,我们旨在使用跨基因组数据来开发精确的PR,并具有多个新颖的跨术统计
方法。我们将开发用于整体乳腺癌及其亚型的PRS模型(雌激素受体阳性
和阴性和三阴性乳腺癌)。然后,我们将验证目标1-2中产生的模型
病例对照研究,正在进行的队列研究的独立数据集(> 14,000例和> 82,000个对照),
以及持续的风险自适应乳腺癌筛查试验。第三,我们将整合表现最佳的PR
现有的风险预测模型基于非基因风险因素。由此产生的绝对风险
模型具有从GWAS转化知识的良好潜力,以告知遗传咨询实践,
非裔美国人的乳腺癌筛查和预防。它具有良好的潜力来提高种族平等
乳腺癌。
项目成果
期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria.
美国和尼日利亚非洲和欧洲血统人群乳腺癌的种系变异和体细胞突变特征。
- DOI:10.1002/ijc.32498
- 发表时间:2019
- 期刊:
- 影响因子:6.4
- 作者:Wang,Shengfeng;Pitt,JasonJ;Zheng,Yonglan;Yoshimatsu,ToshioF;Gao,Guimin;Sanni,Ayodele;Oluwasola,Olayiwola;Ajani,Mustapha;Fitzgerald,Dominic;Odetunde,Abayomi;Khramtsova,Galina;Hurley,Ian;Popoola,Abiodun;Falusi,Adeyinka;Ogundira
- 通讯作者:Ogundira
Validation of the Nigerian Breast Cancer Study Model for Predicting Individual Breast Cancer Risk in Cameroon and Uganda.
- DOI:10.1158/1055-9965.epi-22-0869
- 发表时间:2023-01-09
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.
- DOI:10.1038/s41467-021-27079-w
- 发表时间:2021-11-26
- 期刊:
- 影响因子:16.6
- 作者:Ansari-Pour N;Zheng Y;Yoshimatsu TF;Sanni A;Ajani M;Reynier JB;Tapinos A;Pitt JJ;Dentro S;Woodard A;Rajagopal PS;Fitzgerald D;Gruber AJ;Odetunde A;Popoola A;Falusi AG;Babalola CP;Ogundiran T;Ibrahim N;Barretina J;Van Loo P;Chen M;White KP;Ojengbede O;Obafunwa J;Huo D;Wedge DC;Olopade OI
- 通讯作者:Olopade OI
An enhancer variant associated with breast cancer susceptibility in Black women regulates TNFSF10 expression and antitumor immunity in triple-negative breast cancer.
- DOI:10.1093/hmg/ddac168
- 发表时间:2023-01-01
- 期刊:
- 影响因子:3.5
- 作者:
- 通讯作者:
Benign breast disease and breast cancer risk in African women: A case-control study.
非洲女性的良性乳腺疾病和乳腺癌风险:病例对照研究。
- DOI:10.21203/rs.3.rs-3301977/v1
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Omoleye,OlasubomiJ;Freeman,JincongQ;Oluwasanu,Mojisola;Adeniji-Sofoluwe,Adenike;Woodard,AnnaE;Aribisala,BenjaminS;Adejumo,PriscaO;Ntekim,Atara;Makumbi,Timothy;Ndom,Paul;Ajayi,IkeOluwapoO;Olopade,OlufunmilayoI;Huo,Dezheng
- 通讯作者:Huo,Dezheng
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{{ truncateString('Dezheng Huo', 18)}}的其他基金
Etiology and Genomics of Breast Cancer Progression in Women of African Ancestry
非洲裔女性乳腺癌进展的病因学和基因组学
- 批准号:
10399437 - 财政年份:2019
- 资助金额:
$ 51.53万 - 项目类别:
Etiology and Genomics of Breast Cancer Progression in Women of African Ancestry
非洲裔女性乳腺癌进展的病因学和基因组学
- 批准号:
10610884 - 财政年份:2019
- 资助金额:
$ 51.53万 - 项目类别:
Identifying Barriers for Slow Update of Effective Radiotherapy Method for Cancer
确定有效癌症放射治疗方法更新缓慢的障碍
- 批准号:
9750676 - 财政年份:2018
- 资助金额:
$ 51.53万 - 项目类别:
UChicago Interdisciplinary Cancer Health Disparities SPORE
芝加哥大学跨学科癌症健康差异 SPORE
- 批准号:
10175869 - 财政年份:2018
- 资助金额:
$ 51.53万 - 项目类别:
Using Genomics to Reduce Breast Cancer Disparities in the African Diaspora
利用基因组学减少非洲侨民的乳腺癌差异
- 批准号:
8298031 - 财政年份:2012
- 资助金额:
$ 51.53万 - 项目类别:
MicroRNAs As Novel Biomarkers For Detection of Triple-Negative Breast Cancer
MicroRNA 作为检测三阴性乳腺癌的新型生物标志物
- 批准号:
8243813 - 财政年份:2012
- 资助金额:
$ 51.53万 - 项目类别:
MicroRNAs As Novel Biomarkers For Detection of Triple-Negative Breast Cancer
MicroRNA 作为检测三阴性乳腺癌的新型生物标志物
- 批准号:
8521186 - 财政年份:2012
- 资助金额:
$ 51.53万 - 项目类别:
Using Genomics to Reduce Breast Cancer Disparities in the African Diaspora
利用基因组学减少非洲侨民的乳腺癌差异
- 批准号:
8976663 - 财政年份:2012
- 资助金额:
$ 51.53万 - 项目类别:
Using Genomics to Reduce Breast Cancer Disparities in the African Diaspora
利用基因组学减少非洲侨民的乳腺癌差异
- 批准号:
8513943 - 财政年份:2012
- 资助金额:
$ 51.53万 - 项目类别:
Replication Study of Breast Cancer Susceptibility Genes in Blacks
黑人乳腺癌易感基因的复制研究
- 批准号:
8100727 - 财政年份:2009
- 资助金额:
$ 51.53万 - 项目类别:
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