Hereditary Genetics of Hepatocellular Carcinoma
肝细胞癌的遗传遗传学
基本信息
- 批准号:10632953
- 负责人:
- 金额:$ 51.03万
- 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:2022-07-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAgeAge of OnsetAlcohol consumptionAlcoholsAmericanAnimal ModelBRCA2 geneCHEK2 geneChronicCirrhosisClinicalConfidence IntervalsDNA DamageDNA RepairDNA Repair GeneDNA Sequence AlterationDataDefectDemographic FactorsDevelopmentDiagnosisEnrollmentEnvironmental Risk FactorExposure toFANCD2 proteinFamilyFamily Cancer HistoryFamily history ofFamily memberFanconi Anemia Complementation Group A ProteinFatty LiverFibrinogenFirst Degree RelativeGene ExpressionGene MutationGenesGeneticGenetic ModelsGerm-Line MutationGoalsHepatitis BHepatitis CHereditary Malignant NeoplasmHereditary Neoplastic SyndromesHistologicIndividualInheritedInstitutionInvestigationLinkLiver neoplasmsLoss of HeterozygosityMSH6 geneMalignant NeoplasmsMalignant neoplasm of liverMedical GeneticsMedical centerMutationOdds RatioOncogenesOutcomePMS2 genePathogenesisPathogenicityPatient CarePatientsPersonsPharmacotherapyPilot ProjectsPlayPopulationPopulation ControlPredispositionPrimary carcinoma of the liver cellsProteinsRaceRecording of previous eventsRiskRisk FactorsRoleSamplingShapesStainsTest ResultTestingTimeToxic Environmental SubstancesTumor TissueVenous blood samplingVirus Diseasesbasecancer riskcancer typecarcinogenesiscase controlclinical centerearly onsetexome sequencingfatty liver diseasegene functiongene panelgene repairgenetic associationgenetic testinggenomic locushigh riskhomologous recombinationinhibitorliver cancer modelloss of functionmedical schoolsmortalitypatient subsetspersonalized medicineprecision drugsprospectiverecruitrepairedresearch clinical testingresponsetargeted treatmenttreatment strategytumor
项目摘要
PROJECT SUMMARY
Hepatocellular Carcinoma (HCC) is a devastating and prevalent cancer of the liver with high rates of mortality.
Major risk factors include chronic viral infection (hepatitis B or C), fatty liver disease, alcohol use, and exposure
to environmental toxins. An independent risk factor is a family history of HCC in a first degree relative, which
raises the risk by more than 2.5-fold. However, despite evidence of familial risk, few links to hereditary cancer
syndromes have been identified. It is also not clear whether inherited gene mutations play a pathogenic role in
HCC development, or whether they could be used to guide treatment. We have pioneered an investigation into
inherited (i.e. germline) genetic factors associated with HCC. We have prospectively enrolled 220 patients with
HCC from our medical center for clinical-grade genetic testing. We have recorded the details of their personal
and family cancer history, risk factors, and outcomes. In our pilot analysis, we found a surprisingly high rate of
pathogenic germline mutations in cancer-associated genes in patients with HCC, including numerous mutations
in DNA damage response genes required for homologous repair (HR-DDR). In Aim 1, we will conduct a genetic
association study that is powered to detect clinically meaningful germline mutations linked to HCC, and we will
examine whether hereditary cancer syndromes are more common in persons who developed early onset HCC
or have a family history of cancer. In Aim 2, we will explore the mechanism of HCC arising from defects in HR-
DDR genes, and determine the implications for targeted therapies. These unique studies of the hereditary
genetics of HCC have the potential to personalize therapies for the subset of patients with hereditary cancer
syndromes. We have assembled a team of experts in HCC, hereditary genetics, and animal models to complete
this investigation. This study has the potential to shape the care of patients with HCC in the US and worldwide.
项目总结
肝细胞癌是一种严重危害人类健康的常见肝癌,死亡率高。
主要危险因素包括慢性病毒感染(乙肝或丙型肝炎)、脂肪肝、饮酒和接触
环境毒素。一个独立的危险因素是肝细胞癌的一级亲属的家族史,
使风险增加2.5倍以上。然而,尽管有家族性风险的证据,但很少与遗传性癌症有关
症状已经被识别出来。目前也不清楚遗传基因突变是否起到致病作用。
肝癌的发展,或者它们是否可以被用来指导治疗。我们已经率先调查了
与肝细胞癌相关的遗传性(即生殖系)遗传因素。我们前瞻性地招募了220名患有
从我们的医学中心进行临床级基因检测。我们已经记录了他们个人的详细情况
以及家族癌症病史、危险因素和结果。在我们的试点分析中,我们发现令人惊讶的高比率
肝细胞癌患者肿瘤相关基因的致病胚系突变,包括大量突变
同源修复所需的DNA损伤反应基因(HR-DDR)。在目标1中,我们将进行一项基因
一项旨在检测与肝细胞癌相关的具有临床意义的种系突变的协会研究,我们将
检查遗传性癌症综合征是否在早期发病的肝癌患者中更为常见
或者有癌症家族史。在目标2中,我们将探讨由HR-1缺陷引起的肝癌的机制。
DDR基因,并确定靶向治疗的含义。这些关于遗传性的独特研究
肝癌的遗传学有可能使遗传性癌症患者的个人化治疗成为可能
综合症。我们已经组建了一个由肝细胞癌、遗传遗传学和动物模型专家组成的团队来完成
这次调查。这项研究有可能对美国和世界各地的肝癌患者的护理产生影响。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kirk J Wangensteen其他文献
A method for lifelong genetic manipulation of regenerating hepatocytes in mouse
一种对小鼠再生肝细胞进行终身基因操作的方法
- DOI:
10.1038/cr.2008.121 - 发表时间:
2008-08-04 - 期刊:
- 影响因子:25.900
- 作者:
Kirk J Wangensteen;Andrew Wilber;Vincent W Keng;Yixin Chen;Ilze Matise;Laura Wangensteen;Clifford J Steer;R Scott McIvor;David A Largaespada;Xin Wang;Stephen C Ekker - 通讯作者:
Stephen C Ekker
Kirk J Wangensteen的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kirk J Wangensteen', 18)}}的其他基金
相似国自然基金
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
- 批准号:JCZRQN202500010
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
- 批准号:2025JJ70209
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
- 批准号:
- 批准年份:2024
- 资助金额:0 万元
- 项目类别:面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
- 批准号:2023JJ50274
- 批准年份:2023
- 资助金额:0.0 万元
- 项目类别:省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
- 批准号:
- 批准年份:2022
- 资助金额:33 万元
- 项目类别:地区科学基金项目
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
- 批准号:n/a
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
- 批准号:81973577
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
- 批准号:81602908
- 批准年份:2016
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
- 批准号:81501928
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Determining the mechanism of action of cis-acting modifiers on the age of onset of Huntington Disease
确定顺式作用修饰剂对亨廷顿病发病年龄的作用机制
- 批准号:
417256 - 财政年份:2019
- 资助金额:
$ 51.03万 - 项目类别:
Studentship Programs
Effect of age of onset of contraception use on brain functioning.
避孕开始年龄对大脑功能的影响。
- 批准号:
511267-2017 - 财政年份:2017
- 资助金额:
$ 51.03万 - 项目类别:
University Undergraduate Student Research Awards
Non-random occurrence and early age of onset of diverse lymphoid cancers in families supports the existence of genetic risk factors for multiple lymphoid cancers.
家族中多种淋巴癌的非随机发生和发病年龄较早,支持多种淋巴癌存在遗传危险因素。
- 批准号:
347105 - 财政年份:2016
- 资助金额:
$ 51.03万 - 项目类别:
Polish-German Child Bilingualism: The Role of Age of Onset for Long-Term Achievement
波兰-德国儿童双语:发病年龄对长期成就的作用
- 批准号:
277135691 - 财政年份:2015
- 资助金额:
$ 51.03万 - 项目类别:
Research Grants
Bioinformatics strategies to relate age of onset with gene-gene interaction
将发病年龄与基因间相互作用联系起来的生物信息学策略
- 批准号:
9097781 - 财政年份:2015
- 资助金额:
$ 51.03万 - 项目类别:
Early Age-of-Onset AD: Clinical Heterogeneity and Network Degeneration
早期 AD 发病年龄:临床异质性和网络退化
- 批准号:
9212684 - 财政年份:2014
- 资助金额:
$ 51.03万 - 项目类别:
Early Age-of-Onset AD: Clinical Heterogeneity and Network Degeneration
早期 AD 发病年龄:临床异质性和网络退化
- 批准号:
8696557 - 财政年份:2014
- 资助金额:
$ 51.03万 - 项目类别:
Effects of delaying age of onset of binge drinking on adolescent brain development: A proposal to add neuroimaing measures to the CO-Venture Trial.
延迟酗酒的发病年龄对青少年大脑发育的影响:在 CO-Venture 试验中添加神经影像测量的建议。
- 批准号:
267251 - 财政年份:2012
- 资助金额:
$ 51.03万 - 项目类别:
Operating Grants
Stress Effects on Alcohol Consumption: Age of onset and genes in heavy drinkers
压力对饮酒的影响:酗酒者的发病年龄和基因
- 批准号:
8606722 - 财政年份:2012
- 资助金额:
$ 51.03万 - 项目类别:
Marijuana: Neurobiologic Correlates of Age of Onset
大麻:发病年龄的神经生物学相关性
- 批准号:
8644793 - 财政年份:2012
- 资助金额:
$ 51.03万 - 项目类别: