Germline Determinants of Prostate Cancer Evolution
前列腺癌进化的种系决定因素
基本信息
- 批准号:10587968
- 负责人:
- 金额:$ 62.89万
- 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:2023-04-01 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:African ancestryAgeAggressive behaviorAmericanAsian ancestryAsian populationAutopsyBRCA2 MutationBioinformaticsBiological MarkersBiopsyCancer EtiologyCastrationCessation of lifeClinicalDNA RepairDNA sequencingDataData SetDiagnosisDiseaseDisease ResistanceDistantEuropean ancestryEvolutionGenesGeneticGenetic PolymorphismGenomeGenomicsGerm-Line MutationHeritabilityHispanic PopulationsHispanic ancestryIncidenceIndividualIndolentLinkLocal TherapyMalignant NeoplasmsMalignant neoplasm of prostateMedical Care CostsMethodsMolecularMolecular EvolutionMonitorMorbidity - disease rateNewly DiagnosedOdds RatioPathway AnalysisPathway interactionsPatientsPopulationPopulation HeterogeneityProstateProstate-Specific AntigenProstatic NeoplasmsPublishingRectumRiskSample SizeSerumShapesSiteSkin CancerSolidSomatic MutationStratificationTMPRSS2 geneTestingUnited StatesVariantaging populationbiobankcancer diagnosisclinical riskcohortcostdigitalfollow-upgene repairlifetime riskmale healthmennovelpolygenic risk scorerectalrepositoryrisk predictionrisk stratificationserum PSAstandard of caretranscriptometumortumor diagnosiswhole genome
项目摘要
Abstract
Prostate cancer is the most commonly diagnosed non-skin cancer in men, and the second most common cause
of cancer death for men. It is a high-incidence, high-fatality, high-morbidity and high-cost cancer that is growing
increasingly frequent in our aging population. Clinically, the majority of prostate cancers present as indolent, and
are unlikely to significantly influence a man’s health over his lifetime. Nevertheless, a significant number of
prostate tumors are diagnosed while localized but have substantial metastatic potential. Once these colonize
distant sites, they become almost uniformly lethal. Current standard of care for clinical risk-stratification involves
serum abundance of prostate specific antigen (PSA), a digital rectal exam and biopsy. While these are beneficial,
~30-40% of men are over- or under-treated. Therefore, a central problem in prostate cancer remains
understanding this dramatic variability in the aggressiveness of localized prostate cancers. We hypothesize
that the clinical and molecular evolution of localized prostate cancers are shaped by germline genomic
features. Strong preliminary data support this idea. Prostate cancer is the most heritable solid cancer. It shows
strong variability across ancestries, and specific genetic features predict both risk of incidence and disease
aggression. We will test our hypothesis with three complementary aims. Aim #1 quantifies germline-somatic
interactions using transcriptome-wide association studies (TWAS) and pathway-somatic interaction analysis.
Aim #2 then identifies ancestry-based germline-somatic interactions. Finally Aim #3 will assess the
generalizability of germline-somatic interactions for clinical risk prediction by developing a targeted DNA-
sequencing panel and evaluating biomarker potential in large patient cohorts. To achieve these aims, we will
leverage publicly available datasets as well as biobanking repositories at UCLA, linked to both established and
novel bioinformatics methods. Together, these aims provide three complementary strategies to quantify how the
specific clinical and molecular evolutionary features of localized prostate cancer are influenced by specific
germline polymorphisms.
摘要
前列腺癌是男性最常见的非皮肤癌,也是第二常见的原因
男性的癌症死亡率。它是一种高发、高病死、高致残和高费用的癌症,且呈增长趋势
在我们的老龄化人口中越来越常见。临床上,大多数前列腺癌表现为惰性,
不太可能在一个人的一生中对他的健康产生重大影响。然而,大量的
前列腺肿瘤在局部化时被诊断,但具有实质性的转移潜力。一旦它们殖民
在遥远的地方,它们几乎都是致命的。目前临床风险分层的标准治疗包括
前列腺特异性抗原(PSA)血清丰度,直肠指检和活检。虽然这些都是有益的,
大约30-40%的男性接受了过度或不足的治疗。因此,前列腺癌的一个中心问题仍然是
了解局限性前列腺癌侵袭性的巨大差异。我们假设
局限性前列腺癌的临床和分子进化是由生殖细胞基因组决定的,
功能.强有力的初步数据支持这一观点。前列腺癌是遗传性最强的实体癌。它显示
不同血统之间的强烈变异性和特定的遗传特征可以预测发病率和疾病的风险
侵略我们将用三个互补的目标来检验我们的假设。目标#1量化生殖细胞-体细胞
使用全转录组关联研究(TWAS)和途径-体细胞相互作用分析进行相互作用。
目标#2然后确定基于祖先的生殖系-体细胞相互作用。最后,目标#3将评估
通过开发一种靶向的DNA,
测序面板和评估生物标志物的潜力,在大型患者队列。为达致这些目标,我们会
利用公开可用的数据集以及加州大学洛杉矶分校的生物库存储库,与已建立的
新的生物信息学方法。总之,这些目标提供了三个互补的战略,以量化
局限性前列腺癌的特定临床和分子进化特征受特定
生殖系多态性
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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Paul Christopher Boutros其他文献
Paul Christopher Boutros的其他文献
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{{ truncateString('Paul Christopher Boutros', 18)}}的其他基金
Virginia-UCLA-Toronto Biomarker Characterization Center
弗吉尼亚-加州大学洛杉矶分校-多伦多生物标志物表征中心
- 批准号:
10696069 - 财政年份:2022
- 资助金额:
$ 62.89万 - 项目类别:
Randomized Trial of Exercise Therapy on Markers of Progression in Localized Prostate Cancer:
运动疗法对局限性前列腺癌进展标志物的随机试验:
- 批准号:
10705201 - 财政年份:2022
- 资助金额:
$ 62.89万 - 项目类别:
The Evolution of Sarcoma Drug Sensitivity through Time and Space
肉瘤药物敏感性随时间和空间的演变
- 批准号:
10202513 - 财政年份:2020
- 资助金额:
$ 62.89万 - 项目类别:
The Evolution of Sarcoma Drug Sensitivity through Time and Space
肉瘤药物敏感性随时间和空间的演变
- 批准号:
10434822 - 财政年份:2020
- 资助金额:
$ 62.89万 - 项目类别:
The Evolution of Sarcoma Drug Sensitivity through Time and Space
肉瘤药物敏感性随时间和空间的演变
- 批准号:
10778672 - 财政年份:2020
- 资助金额:
$ 62.89万 - 项目类别:
The Evolution of Sarcoma Drug Sensitivity through Time and Space
肉瘤药物敏感性随时间和空间的演变
- 批准号:
10646502 - 财政年份:2020
- 资助金额:
$ 62.89万 - 项目类别:
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