Urinary DNA Adductomics for the Assessment of Exposure to Cancer Risk Factors
用于评估癌症危险因素暴露情况的尿液 DNA 加合物组学
基本信息
- 批准号:10740573
- 负责人:
- 金额:$ 1.45万
- 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:2021-01-30 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAgingBenzeneCancer EtiologyCell physiologyDNADNA DamageDiseaseEnvironmentEnvironmental CarcinogensEnvironmental ExposureEvaluation of Cancer Risk FactorsExposure toGenomeHealthHumanInvestigationKnowledgeLeadMalignant NeoplasmsMapsMutagensMutationMutation AnalysisParentsPathologic MutagenesisPatientsPatternPilot ProjectsProcessRiskRisk FactorsRoleRouteTestingadductcancer riskcarcinogenesisenvironmental agentgenome sequencingnoveloxidationtumorurinarywhole genome
项目摘要
PROJECT SUMMARY
Environmental genotoxin exposure is responsible for 80-90% of the risk of developing cancer. Indeed, Whole
Genome Sequencing studies show that human cancers carry mutational signatures reflective of the
environmental agents to which the patients were exposed. However, some studies suggest that many mutational
signatures arise from endogenous cellular processes. Mutations can arise when DNA is modified/damaged by
exogenous physicochemical agents and endogenous cellular processes (e.g., oxidation). Agent-specific
mutational signatures of environmental carcinogens reveal similarities to those found in human tumors. However,
more common are the mutations related to endogenous processes known as ageing signatures i.e., SBS1 and
SBS5. Understanding the origins of these signatures, which is key to a better understanding of cancer causes,
requires a comprehensive approach to studying adducts. DNA adductomics aims to describe the totality of
adducts in the genome, which are implicated in carcinogenesis. We hypothesize that exogenous agents act, at
least in part, via the induction of signature patterns or types of adducts, but additionally they may also influence
endogenous mutagenic processes, altering the DNA adductome. The aberrant alteration of endogenous
processes would account for the low level of agent-specific mutations in tumors despite strong evidence for the
key role of environmental agents in carcinogenesis. To begin to test this hypothesis, we will perform pilot studies
to address the following aims: Aim 1, evaluate the impact of the endogenous DNA adductome upon the
corresponding mutational landscape. In Aim 2, evaluate the impact of an exogenous environmental exposure
(benzene) upon the endogenous DNA adductome, and corresponding mutational landscape. Analysis of the
mutational landscapes, and their corresponding DNA adductome maps, will begin to advance our understanding
of the relationships between the exposome, DNA adductome and mutatome, and hence enhance the results of
the parent R01. Pursuing this route of investigation will pave the way for the identification/evaluation of cancer
risk factors and the identification of novel mutational signatures caused by exogenous/endogenous exposures.
项目总结
环境中的基因毒素暴露导致了80%-90%的癌症风险。事实上,整个
基因组测序研究表明,人类癌症携带的突变特征反映了
患者所接触到的环境因素。然而,一些研究表明,许多突变
签名源于内源性的细胞过程。当DNA被修改/损坏时,可能会发生突变
外源性的物理化学物质和内源性的细胞过程(如氧化)。特定于代理的
环境致癌物的突变特征揭示了与人类肿瘤中发现的相似之处。然而,
更常见的是与内源性过程有关的突变,称为衰老特征,即SBS1和
SBS5.了解这些特征的起源,这是更好地理解癌症原因的关键,
需要一个全面的方法来研究加合物。DNA吸引学的目的是描述
基因组中的加合物,它们与癌症的发生有关。我们假设外源因子在
至少部分地通过诱导签名模式或加合物类型,但另外它们也可能影响
内源性突变过程,改变DNA加合物组。内源性的异常变化
尽管有强有力的证据表明,肿瘤中毒剂特异性突变的水平较低,但这一过程将解释
环境因素在癌症发生中的关键作用。为了开始检验这一假设,我们将进行初步研究
为解决以下目标:目标1,评估内源DNA加合物组对
相应的变异景观。在目标2中,评估外源环境暴露的影响
(苯)在内源DNA加合物组上,以及相应的突变景观。三、分析了
突变的景观及其相应的DNA加合物组图谱将开始推进我们对
暴露组、DNA加合物组和突变组之间的关系,从而增强
父R01。进行这一研究将为癌症的识别/评估铺平道路。
风险因素和由外源性/内源性暴露引起的新突变特征的识别。
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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Marcus Stanley Cooke其他文献
Marcus Stanley Cooke的其他文献
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{{ truncateString('Marcus Stanley Cooke', 18)}}的其他基金
Urinary DNA Adductomics for the Assessment of Exposure to Cancer Risk Factors
用于评估癌症危险因素暴露情况的尿液 DNA 加合物组学
- 批准号:
10506391 - 财政年份:2022
- 资助金额:
$ 1.45万 - 项目类别:
Urinary DNA Adductomics for the Assessment of Exposure to Cancer Risk Factors
用于评估癌症危险因素暴露情况的尿液 DNA 加合物组学
- 批准号:
10336865 - 财政年份:2021
- 资助金额:
$ 1.45万 - 项目类别:
Urinary DNA Adductomics for the Assessment of Exposure to Cancer Risk Factors
用于评估癌症危险因素暴露情况的尿液 DNA 加合物组学
- 批准号:
10362717 - 财政年份:2021
- 资助金额:
$ 1.45万 - 项目类别:
Urinary DNA Adductomics for the Assessment of Exposure to Cancer Risk Factors
用于评估癌症危险因素暴露情况的尿液 DNA 加合物组学
- 批准号:
10763603 - 财政年份:2021
- 资助金额:
$ 1.45万 - 项目类别:
Urinary DNA Adductomics for the Assessment of Exposure to Cancer Risk Factors
用于评估癌症危险因素暴露情况的尿液 DNA 加合物组学
- 批准号:
10544501 - 财政年份:2021
- 资助金额:
$ 1.45万 - 项目类别:
Urinary DNA Adductomics for the Assessment of Exposure to Cancer Risk Factors
用于评估癌症危险因素暴露情况的尿液 DNA 加合物组学
- 批准号:
9901533 - 财政年份:2019
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Genomic instability, susceptibility to oxidative stress and cellular senescence
基因组不稳定、对氧化应激和细胞衰老的易感性
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9304443 - 财政年份:2017
- 资助金额:
$ 1.45万 - 项目类别:
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