Living beyond cancer: the short- and long-term cognitive effects of breast cancer and its treatment for cancer survivors
超越癌症的生活:乳腺癌的短期和长期认知影响及其对癌症幸存者的治疗
基本信息
- 批准号:10570360
- 负责人:
- 金额:$ 13.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-12-15 至 2027-11-30
- 项目状态:未结题
- 来源:
- 关键词:ABCB1 geneAccelerationAddressAdherenceAffectAftercareAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease patientAntineoplastic AgentsAreaAttenuatedBrainBreast Cancer TreatmentBreast Cancer survivorCancer EtiologyCancer SurvivorCancer SurvivorshipCaringClinical ResearchCognitionCognitiveDiagnosisDiagnosticDiseaseDrug TransportElderlyEpidemiologyEtiologyGene ExpressionGenesGeneticGenetic PolymorphismGenomic InstabilityGenomicsGoalsHealthy EatingHeritabilityHumanImpaired cognitionIncidenceInflammationInterdisciplinary StudyInterventionInvestigationJointsLife StyleLong-Term EffectsMalignant NeoplasmsMammary NeoplasmsMeasuresMediterranean DietMitochondriaMolecularMutationNurses&apos Health StudyObservational StudyOxidative StressPathway interactionsPharmaceutical PreparationsPhysical activityPopulationPopulation StudyPositioning AttributeProliferatingQuality of lifeRadiationRadiation therapyRecording of previous eventsRegulationReportingResearchResearch PersonnelResourcesRiskRoleStatistical ModelsStrategic visionSubgroupSurvival RateSurvivorsTP53 geneTamoxifenTimeToxicity due to chemotherapyTrainingWomanacute toxicityaging brainaging populationanticancer researchblood-brain barrier crossingbrain tissuebreast cancer diagnosiscancer carecancer diagnosiscancer therapychemobrainchemotherapycognitive functioncognitive testingexperiencefollow-upgenetic analysisgood diethigh riskhormone receptor-negativehormone therapyhuman old age (65+)improvedindexingmalignant breast neoplasmmolecular subtypesneural repairoxidationpluripotencypreventprospectiverisk predictionskill acquisitiontraittranscriptomics
项目摘要
PROJECT SUMMARY
With the rapidly aging population and improved survival rate, the number of breast cancer survivors in the U.S.
is projected to reach 4.4 million by 2030, among which more than 60% of them will be aged ≥65 years. A key
issue facing older cancer survivors is the impact of cancer and its treatment on their cognition. Cancer and brain
aging have both common and distinct etiologies. For example, shared germline genetic heritability was identified
between breast cancer and Alzheimer’s disease (AD) in large cross-trait genetic analyses, while other studies
showed differential regulation of p53 and Pin1 in cancer and AD. Compelling clinical and observational studies
report deficits in cognitive functioning in women diagnosed and treated for breast cancer over the short-term (<2
years), and consistently support acute toxicity of chemotherapies on cognition (i.e., chemo-brain). In contrast,
population studies, often with long follow-up (>10 years), show lower incidence of AD in cancer survivors
compared with cancer-free controls. While these inverse associations have persisted in studies with attempts to
reduce diagnostic and competing risk biases, the possibility of survival bias, which would increase with time
since cancer diagnosis, cannot be ruled out. Until we can determine how breast cancer and its treatment
(chemotherapy, radiation, and hormone therapy) affect cognitive trajectory, we will not be able to improve quality
of life and care for breast cancer survivors. However, most previous research is limited by a lack of (a)
consideration of both the short- and long-term effect of breast cancer on cognition (which may reduce survival
bias for breast cancer with a 5-year relative survival rate of 90%); (b) repeated global and domain specific
cognition measures before and after treatment; (c) focus on the role of post-diagnostic lifestyles in the treatment-
cognition relation; (d) investigation of gene-treatment interactions; (e) and identification of shared and distinct
molecular etiologies of cancer and AD. The overarching goal of this proposal is to comprehensively determine
the association of breast cancer diagnosis and treatment with cognitive trajectory over time, and identify the
intersection of cancer hallmark pathways with AD to inform targeted intervention. This proposal leverages the
unique resources from the Nurses’ Health Study with follow-up of 3,120 breast cancer survivors for >30 years,
and repeatedly collected objective cognitive assessments; and the Gene Expression Omnibus with 2,520 human
brain transcriptomics on AD patients and controls, and addresses the following hypothesis: (1) Women
diagnosed and treated with cancer experience more rapid cognitive decline over the short-term, and (2) Cancer
hallmarks of genomic instability, oxidative stress and inflammation are shared mechanisms between cancer and
AD, but the hallmarks of proliferation and cellular pluripotency are differentially regulated. Dr. Peng plans to
receive training in areas of aging research, cancer survivorship, advanced statistical modeling, and professional
skill development. Together, the scientific and training components of this K01 will position Dr. Peng to become
an independent interdisciplinary investigator specialized in the integration of aging and cancer research.
项目概要
随着人口的迅速老龄化和生存率的提高,美国乳腺癌幸存者的数量不断增加。
预计到2030年将达到440万,其中60%以上年龄≥65岁。
老年癌症幸存者面临的问题是癌症及其治疗对他们认知的影响。
衰老有共同的和不同的病因,例如,共同的种系遗传性已被确定。
在大型跨性状遗传分析中,乳腺癌和阿尔茨海默病 (AD) 之间存在差异,而其他研究
显示了 p53 和 Pin1 在癌症和 AD 中的差异调节。
报告短期内诊断和治疗乳腺癌的女性认知功能缺陷(<2
年),并始终支持化疗对认知(即化疗脑)的急性毒性。
通常进行长期随访(>10 年)的人群研究表明,癌症幸存者 AD 的发病率较低
与无癌症对照相比,尽管这些反向关联在试图研究的研究中仍然存在。
减少诊断和竞争风险偏差以及生存偏差的可能性,这种偏差会随着时间的推移而增加
自癌症诊断以来,在我们确定如何治疗乳腺癌之前,不能排除这种可能性。
(化疗、放疗和激素治疗)影响认知轨迹,我们将无法提高质量
然而,大多数先前的研究都因缺乏(a)而受到限制。
考虑乳腺癌对认知的短期和长期影响(这可能会降低生存率)
乳腺癌的偏倚,5 年相对生存率为 90%)(b)重复的全球和特定领域;
治疗前和治疗后的认知测量;(c)关注诊断后生活方式在治疗中的作用
认知关系;(d) 基因治疗相互作用的调查;(e) 共同和独特的识别;
该提案的总体目标是全面确定癌症和 AD 的分子病因。
随着时间的推移,乳腺癌诊断和治疗与认知轨迹的关联,并确定
该提案利用了癌症标志通路与 AD 的交叉点来指导有针对性的干预。
来自护士健康研究的独特资源,对 3,120 名乳腺癌幸存者进行了超过 30 年的跟踪调查,
并反复收集 2,520 人的客观认知评估;以及基因表达综合数据
AD 患者和对照组的脑转录组学研究,并提出以下假设:(1) 女性
诊断和治疗癌症的人在短期内认知能力下降更快,以及 (2) 癌症
基因组不稳定、氧化应激和炎症的标志是癌症和癌症之间的共同机制。
AD,但彭博士计划对增殖和细胞多能性进行差异化调控。
接受衰老研究、癌症生存、高级统计模型和专业领域的培训
K01 的科学和培训部分将使彭博士成为技能发展者。
一位独立的跨学科研究者,专门从事衰老和癌症研究的整合。
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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Cheng Peng其他文献
Improved IFDMA Transmission Structure on SISO and MISO Channels
SISO 和 MISO 通道上改进的 IFDMA 传输结构
- DOI:
10.1587/transcom.e93.b.2203 - 发表时间:
- 期刊:
- 影响因子:0
- 作者:
Xiao Yue;Cheng Peng;He Xu;Li Shaoqian - 通讯作者:
Li Shaoqian
Comparison of reversed-phase liquid chromatography and hydrophilic interaction chromatography for the fingerprint analysis of Radix isatidis
反相液相色谱法与亲水相互作用色谱法板蓝根指纹图谱分析比较
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:0
- 作者:
Lina Ma;Cheng Peng;Xiaoping Dong;Dan Yan - 通讯作者:
Dan Yan
Cheng Peng的其他文献
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