TGF-beta pathway polymorphisms and colon cancer risk
TGF-β途径多态性与结肠癌风险
基本信息
- 批准号:7350209
- 负责人:
- 金额:$ 12.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-02-24 至 2008-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAlanineAllelesAmino AcidsAnimal ModelAreaAspirinBindingBreastCancer FamilyCase-Control StudiesCell surfaceCodeColonColon CarcinomaColorectalColorectal CancerComplexDataDefectDiseaseDisease AssociationDoctor of PhilosophyDoseEnvironmental ExposureEpithelial CellsFamily-Based RegistryFoundationsFrequenciesGCG geneGene FrequencyGenesGeneticGenetic PolymorphismGenotypeGenus ColaGlucagonGrowthGrowth InhibitorsHaplotypesHeterozygoteHomozygoteHumanIn VitroIncidenceIndividualInheritedIntervention TrialLaboratoriesLeadLeucineLigandsMalignant NeoplasmsMalignant neoplasm of ovaryMediatingMedicalMeta-AnalysisMicrosatellite InstabilityMorbidity - disease rateNon-Steroidal Anti-Inflammatory AgentsPathogenesisPathway interactionsPatientsPatternPenetrancePositioning AttributePredispositionPrincipal InvestigatorProlineRegistriesResearchResearch PersonnelResourcesRiskSiblingsSignal PathwaySignal TransductionTGFB1 geneTGFBR1 geneTGFBR2 geneTestingTransforming Growth Factor betaTriplet Multiple BirthVariantWorkcancer diagnosiscancer riskcancer typecarcinogenesiscase controlcell growthdesignextracellulargene interactiongenetic epidemiologyin vivointerestmortalityneoplasm registryprogramsreceptorreceptor bindingtumor
项目摘要
We have previously identified TGFBR1*6A, a common variant of the TGFBR1 gene, and shown that it transmits TGF-a growth inhibitory signals less effectively than TGFBR1. Our recent meta-analyses show that TGFBR1*6A carriers have a significantly increased risk of colon, breast and ovarian cancer as compared with non-carriers. Overall, cancer risk is increased by 19% among heterozygotes and 70% among homozygotes, a pattern indicative of an allelic dosing effect. We have also shown that TGFBR1*6A may contribute to hereditary colorectal cancer. More than one in eight healthy individuals and one in six patients with cancer is a TGFBR1*6A carrier, which establishes TGFBR1*6A as the first high-frequency low-penetrance candidate tumor susceptibility allele. In contrast, increased TGF-a circulating levels have been associated with a decreased cancer risk in animal models. A common Leucine to Proline substitution at the 10th amino acid position variant within the human TGF- a1 (TGFB1) gene results in higher in vitro extracellular TGFB1 secretion. Carriers of the TGFB1*CC genotype have higher in vivo TGFB1 circulating levels than carriers of the TGFB1*TT genotype. TGFBR1 and TGFB1 variants my have opposite or synergistic effects on colorectal cancer risk. Our central hypothesis is that a combined assessment of the two functionally-relevant TGF- a pathway signaling variants will predict colorectal cancer risk more accurately than each variant alone. The NCI-sponsored familial colorectal cancer registry is an ideal resource in which to test this hypothesis. Using a sibling-matched case-control design we will genotype a total of 4,208 full sibling case-control pairs and First: assess the association between TGFBR1*6A and colorectal cancer. Second: assess the association between TGFB1 and colorectal cancer and perform haplotype analysis of the TGFB1 gene; Third: analyze gene-gene interactions between TGFBR1 and TGFB1. This will explore the relationships between the two functional TGF-a pathway polymorphisms and colorectal risk and determine whether TGF- a signaling, as predicted by these two variants, is associated with colorectal cancer risk; and, Fourth: investigate the relationship between TGF-a pathway polymorphisms and tumor microsatellite instability.
我们先前已经鉴定了TGFBR 1 *6A,这是TGFBR 1基因的一种常见变体,并表明它传递TGF-α生长抑制信号的效率低于TGFBR 1。我们最近的荟萃分析显示,与非携带者相比,TGFBR 1 *6A携带者患结肠癌、乳腺癌和卵巢癌的风险显著增加。总的来说,杂合子中癌症风险增加了19%,纯合子中增加了70%,这是一种等位基因剂量效应的模式。我们还发现TGFBR 1 *6A可能与遗传性结直肠癌有关。超过八分之一的健康个体和六分之一的癌症患者是TGFBR 1 *6A携带者,这确立了TGFBR 1 *6A作为第一个高频低突变候选肿瘤易感等位基因。相反,在动物模型中,增加的TGF-α循环水平与降低的癌症风险相关。在人TGF-α 1(TGFB 1)基因内的第10个氨基酸位置变体处的常见亮氨酸至脯氨酸取代导致体外细胞外TGFB 1分泌更高。TGFB 1 *CC基因型携带者体内TGFB 1循环水平高于TGFB 1 *TT基因型携带者。TGFBR 1和TGFB 1变体可能对结直肠癌风险具有相反或协同作用。我们的中心假设是,两种功能相关的TGF-α途径信号传导变体的组合评估将比单独的每种变体更准确地预测结直肠癌风险。NCI发起的家族性结直肠癌登记是检验这一假设的理想资源。使用同胞配对病例对照设计,我们将对总共4,208个完全同胞病例对照对进行基因分型,首先:评估TGFBR 1 *6A与结直肠癌之间的关联。第二个:评估TGFB 1与结直肠癌之间的关联,并进行TGFB 1基因的单倍型分析;第三,分析TGFB 1和TGFB 1之间的基因-基因相互作用。这将探索两种功能性TGF-α途径多态性与结直肠癌风险之间的关系,并确定这两种变体预测的TGF-α信号传导是否与结直肠癌风险相关;第四:研究TGF-α途径多态性与肿瘤微卫星不稳定性之间的关系。
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 }}
Boris Pasche其他文献
Boris Pasche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('Boris Pasche', 18)}}的其他基金
Administrative Supplements for the NCI P30 Cancer Center Support Grants for Multi-Channel Communication Campaigns for Improvements in Cancer Education and Outcomes (MICEO) in Underserved Populations
NCI P30 癌症中心行政补充,支持多渠道沟通活动,以改善服务不足人群的癌症教育和结果 (MICEO)
- 批准号:
10891877 - 财政年份:2022
- 资助金额:
$ 12.65万 - 项目类别:
Role of TGF-Beta Genetic Variants in the Pathogenesis of Scleroderma
TGF-β 基因变异在硬皮病发病机制中的作用
- 批准号:
7665023 - 财政年份:2008
- 资助金额:
$ 12.65万 - 项目类别:
Role of TGF-Beta Genetic Variants in the Pathogenesis of Scleroderma
TGF-β 基因变异在硬皮病发病机制中的作用
- 批准号:
7267285 - 财政年份:2007
- 资助金额:
$ 12.65万 - 项目类别:
TGF-beta pathway polymorphisms and colon cancer risk
TGF-β途径多态性与结肠癌风险
- 批准号:
7189819 - 财政年份:2006
- 资助金额:
$ 12.65万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 12.65万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 12.65万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 12.65万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 12.65万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 12.65万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 12.65万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 12.65万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 12.65万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 12.65万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 12.65万 - 项目类别:
Grant-in-Aid for Early-Career Scientists