Molecular Biomarkers as Predictors of Hodgkin's Disease

分子生物标志物作为霍奇金病的预测因子

基本信息

  • 批准号:
    7240491
  • 负责人:
  • 金额:
    $ 28.67万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-08-01 至 2010-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): A major concern for Hodgkin's Disease (HD) survivors is the development of recurrence or second primary tumors. Although factors responsible for the unfavorable outcomes and poor survival of HD patients remain incompletely understood, the population at highest risk seems to be genetically predisposed. In this proposal we propose to evaluate a panel of susceptibility biomarkers as predictors of disease outcome in an existing cohort of 254 HD patients for whom demographic, epidemiological, clinical data and pretreatment blood samples are available. We will test the hypothesis that unfavorable outcomes occur more frequently in patients with poor DNA repair capacity (measures by increase chromosome instability) and with adverse genotypes (polymorphisms in DNA repair and cell cycle control) as compared with patients with favorable outcome. Specifically we propose: 1) To collect follow-up information on health and vital status data to ascertain endpoints (recurrence or second primary tumors) for all the HD patients in the cohort; 2) To phenotypically characterize the role of background chromosomal instability (measured by chromosome aberrations and sister chromatid exchanges) in disease recurrence or development of SPTs. We hypothesize that patients with poor outcomes exhibit higher levels of baseline chromosomal damage than patients with favorable outcome. 3) To elucidate the role that specific polymorphisms in DNA repair capacity genes (XRCC1, XPD and XRCC3) and cell cycle control (p53 gene) play in the modulation of HD outcome. We hypothesize that individuals with DNA repair allelic variants have altered DNA repair capacity and increased risk of developing recurrence or SPT. Similarly, the allelic variants of p53 gene are associated with variant proteins that may alter cell cycle control encouraging progression either by inducing genomic instability and DNA misrepair or by permitting survival of mutants which will in turn have a negative impact on outcome; and 4) To analyze epidemiological and biomarker data independently and jointly as predictors of recurrence and development of SPTs. Identification of subgroups of HD patients who are at increased risk for recurrence or second primary tumor development has both clinical and prognostic relevance. The high risk population can be targeted for intensive preventive and early detection strategies.
描述(由申请人提供):霍奇金病(HD)幸存者的一个主要问题是复发或第二原发肿瘤的发展。尽管对造成HD患者不良结局和生存率差的因素仍不完全清楚,但高危人群似乎具有遗传易感性。在本提案中,我们建议在现有的254例HD患者队列中评价一组易感性生物标志物作为疾病结局的预测因子,这些患者的人口统计学、流行病学、临床数据和治疗前血液样本可用。我们将检验这样一个假设,即与预后良好的患者相比,DNA修复能力差(通过增加染色体不稳定性来衡量)和基因型不良(DNA修复和细胞周期控制中的多态性)的患者更容易出现不良预后。具体而言,我们建议:1)收集关于健康和生命状态数据的随访信息,以确定队列中所有HD患者的终点(复发或第二原发性肿瘤); 2)表型表征背景染色体不稳定性(通过染色体畸变和姐妹染色单体交换测量)在疾病复发或发生SPT中的作用。我们假设预后不良的患者比预后良好的患者表现出更高水平的基线染色体损伤。3)探讨DNA修复能力基因(XRCC 1、XPD和XRCC 3)和细胞周期调控基因(p53基因)的特异性多态性在HD预后中的作用。我们推测,DNA修复等位基因变异的个体改变了DNA修复能力,增加了复发或SPT的风险。类似地,p53基因的等位基因变体与变体蛋白相关,所述变体蛋白可能通过诱导基因组不稳定性和DNA错误修复或通过允许突变体存活来改变细胞周期控制,从而促进进展,这反过来将对结果产生负面影响;以及4)独立地和联合地分析流行病学和生物标志物数据作为SPT复发和发展的预测因子。确定复发或第二原发性肿瘤发生风险增加的HD患者亚组具有临床和预后相关性。高危人群可作为强化预防和早期发现战略的目标。

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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RANDA A EL-ZEIN其他文献

RANDA A EL-ZEIN的其他文献

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{{ truncateString('RANDA A EL-ZEIN', 18)}}的其他基金

Identify the DNA Adduct and Associated Metabolic Alterations in Bladder Cancer of Smokers
鉴定吸烟者膀胱癌中的 DNA 加合物和相关代谢改变
  • 批准号:
    10371068
  • 财政年份:
    2018
  • 资助金额:
    $ 28.67万
  • 项目类别:
Identify the DNA Adduct and Associated Metabolic Alterations in Bladder Cancer of Smokers
鉴定吸烟者膀胱癌中的 DNA 加合物和相关代谢改变
  • 批准号:
    9895423
  • 财政年份:
    2018
  • 资助金额:
    $ 28.67万
  • 项目类别:
Cross regulation of TGSB/elf, B-catenin and vitamin D pathways in Gastrointestin
胃肠道中 TGSB/elf、B-连环蛋白和维生素 D 途径的交叉调节
  • 批准号:
    8744870
  • 财政年份:
    2013
  • 资助金额:
    $ 28.67万
  • 项目类别:
Validation and extension of an existing risk model for lung cancer
现有肺癌风险模型的验证和扩展
  • 批准号:
    7911887
  • 财政年份:
    2009
  • 资助金额:
    $ 28.67万
  • 项目类别:
Cytokinesis-blocked micronucleus assay: a predictive biomarker of lung cancer ris
细胞分裂阻断微核测定:肺癌风险的预测生物标志物
  • 批准号:
    7532309
  • 财政年份:
    2008
  • 资助金额:
    $ 28.67万
  • 项目类别:
Cytokinesis-blocked micronucleus assay: a predictive biomarker of lung cancer ris
细胞分裂阻断微核测定:肺癌风险的预测生物标志物
  • 批准号:
    7694368
  • 财政年份:
    2008
  • 资助金额:
    $ 28.67万
  • 项目类别:
Molecular Biomarkers as Predictors of Hodgkin's Disease
分子生物标志物作为霍奇金病的预测因子
  • 批准号:
    6777608
  • 财政年份:
    2003
  • 资助金额:
    $ 28.67万
  • 项目类别:
Molecular Biomarkers as Predictors of Hodgkin's Disease
分子生物标志物作为霍奇金病的预测因子
  • 批准号:
    7091635
  • 财政年份:
    2003
  • 资助金额:
    $ 28.67万
  • 项目类别:
Molecular Biomarkers as Predictors of Hodgkin's Disease
分子生物标志物作为霍奇金病的预测因子
  • 批准号:
    6919925
  • 财政年份:
    2003
  • 资助金额:
    $ 28.67万
  • 项目类别:
Molecular Biomarkers as Predictors of Hodgkin's Disease
分子生物标志物作为霍奇金病的预测因子
  • 批准号:
    6680963
  • 财政年份:
    2003
  • 资助金额:
    $ 28.67万
  • 项目类别:

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