Confirmation of SNPs Associated with Aggressive PCa in a GWA Study

GWA 研究中确认与侵袭性 PCa 相关的 SNP

基本信息

  • 批准号:
    7472728
  • 负责人:
  • 金额:
    $ 67.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-04-04 至 2012-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Title: Confirmation of SNPs Associated with Aggressive PCa in a GWA study A genetic predisposition to prostate cancer (PCa) is well established and is the strongest among all common cancers. Inherited sequence variants in a number of genes, each conferring a moderate risk, are believed to collectively underlie the genetic predisposition. To systematically identify these risk variants, we have initiated an ambitious genome-wide association (GWA) study that includes several large and well characterized study populations in Sweden and Johns Hopkins Hospital, totaling > 10,000 cases and controls. Thus far, we have completed the 1st stage of this proposed GWA by studying 550K SNPs, including 20K nonsynonymous SNPs, among 500 aggressive cases and 500 controls from a Swedish population (CAPS). To further improve the power of identifying moderate risk SNPs, we propose a study to considerably increase the sample size for a GWA and systematically follow-up a large number of SNPs among independent study populations. We propose four specific aims to test the hypothesis that inherited sequence variants in the genome may increase or modify PCa risk. Aim 1) As the 2nd stage, we will genotype 500K SNPs and a subset of 50K supplement SNPs among an additional 800 aggressive PCa cases and 800 controls from Sweden. A joint association analysis among subjects in stages 1 & 2 will be performed to select SNPs for further confirmation. Aim 2) As the 3rd stage, we will test for PCa associations for the ~6,500 SNPs among an additional 2,000 aggressive PCa cases and 1,000 controls from Johns Hopkins Hospital. A combined analysis will be performed for these SNPs among all available subjects to identify SNPs that reach genome-wide significance level. Aim 3) Perform a fine mapping analysis at genomic regions surrounding the genome-wide significant SNPs to identify variants that are most strongly associated with PCa risk among all 3,300 aggressive PCa cases and 2,300 controls. Aim 4) Assess association of the PCa risk variants with the disease progression among 5,000 cases with extensive follow-up information from a Swedish Nationwide Follow-Up study of Localized PCa (FU-study) and 500 matched-pairs of progressors and non-progressors from Johns Hopkins Hospital. The identification of PCa risk variants may impact the understanding, prevention, diagnosis, and treatment of this disease. PUBLIC HEALTH RELEVANCE: We propose to identify inherited sequence variants in the genome that confer moderate risk to prostate cancer (PCa) using a genome-wide association (GWA) study among more than 10,000 subjects from multiple study populations. The identified genes may advance our understanding on the etiology of PCa and could be used to better predict the risk for developing PCa. The focus on aggressive PCa is particularly important because this is the most clinically relevant form of PCa.
描述(由申请人提供):标题:GWA研究中与侵袭性PCa相关的SNP的确认前列腺癌(PCa)的遗传易感性已得到充分证实,并且是所有常见癌症中最强的。许多基因中的遗传序列变异,每一个都赋予中度风险,被认为是遗传易感性的共同基础。为了系统地识别这些风险变异,我们启动了一项雄心勃勃的全基因组关联(GWA)研究,该研究包括瑞典和约翰霍普金斯医院的几个大型且特征良好的研究人群,总计> 10,000例病例和对照。到目前为止,我们已经完成了第一阶段的GWA研究550 K单核苷酸多态性,包括20 K非同义单核苷酸多态性,在500例侵略性病例和500名对照瑞典人口(CAPS)。为了进一步提高识别中度风险SNP的能力,我们提出了一项研究,以大大增加GWA的样本量,并在独立的研究人群中系统地随访大量SNP。我们提出了四个具体的目标来检验基因组中遗传序列变异可能增加或改变PCa风险的假设。目的1)作为第二阶段,我们将对来自瑞典的另外800例侵袭性PCa病例和800例对照中的500 K SNP和50 K补充SNP的子集进行基因分型。将在第1和第2阶段的受试者之间进行联合关联分析,以选择SNP进行进一步确认。目的2)作为第三阶段,我们将在来自约翰霍普金斯医院的另外2,000例侵袭性PCa病例和1,000例对照中检测约6,500个SNP的PCa关联。将对所有可用受试者中的这些SNP进行合并分析,以确定达到全基因组显著性水平的SNP。目的3)在全基因组显著SNP周围的基因组区域进行精细作图分析,以在所有3,300例侵袭性PCa病例和2,300例对照中鉴定与PCa风险最强相关的变异。目的4)在来自瑞典全国局部PCa随访研究(FU-研究)的具有广泛随访信息的5,000例病例和来自约翰霍普金斯医院的500对匹配的进展者和非进展者中评估PCa风险变体与疾病进展的关联。PCa风险变异的识别可能会影响对这种疾病的理解、预防、诊断和治疗。公共卫生相关性:我们建议在来自多个研究人群的10,000多名受试者中进行全基因组关联(GWA)研究,以确定基因组中赋予前列腺癌(PCa)中度风险的遗传序列变异。这些基因的发现有助于我们进一步了解前列腺癌的病因,并可用于更好地预测前列腺癌的发病风险。对侵袭性PCa的关注特别重要,因为这是PCa的最临床相关形式。

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(1)

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Jianfeng Xu其他文献

Jianfeng Xu的其他文献

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{{ truncateString('Jianfeng Xu', 18)}}的其他基金

Engineering novel designer biologics in plant cells for oral treatment of ulcerative colitis
在植物细胞中设计新型生物制剂用于口腔治疗溃疡性结肠炎
  • 批准号:
    10202300
  • 财政年份:
    2021
  • 资助金额:
    $ 67.96万
  • 项目类别:
Clinical validity and utility of genomic targeted chemoprevention of PCa
前列腺癌基因组靶向化学预防的临床有效性和实用性
  • 批准号:
    7944011
  • 财政年份:
    2009
  • 资助金额:
    $ 67.96万
  • 项目类别:
Clinical validity and utility of genomic targeted chemoprevention of PCa
前列腺癌基因组靶向化学预防的临床有效性和实用性
  • 批准号:
    7853457
  • 财政年份:
    2009
  • 资助金额:
    $ 67.96万
  • 项目类别:
Confirmation of SNPs Associated with Aggressive PCa in a GWA Study
GWA 研究中确认与侵袭性 PCa 相关的 SNP
  • 批准号:
    7756692
  • 财政年份:
    2008
  • 资助金额:
    $ 67.96万
  • 项目类别:
Confirmation of SNPs Associated with Aggressive PCa in a GWA Study
GWA 研究中确认与侵袭性 PCa 相关的 SNP
  • 批准号:
    8015277
  • 财政年份:
    2008
  • 资助金额:
    $ 67.96万
  • 项目类别:
Confirmation of SNPs Associated with Aggressive PCa in a GWA Study
GWA 研究中确认与侵袭性 PCa 相关的 SNP
  • 批准号:
    7603059
  • 财政年份:
    2008
  • 资助金额:
    $ 67.96万
  • 项目类别:
QTL mapping for genes regulating apoptosis capacity
调控细胞凋亡能力基因的QTL定位
  • 批准号:
    7904112
  • 财政年份:
    2006
  • 资助金额:
    $ 67.96万
  • 项目类别:
QTL mapping for genes regulating apoptosis capacity
调控细胞凋亡能力基因的QTL定位
  • 批准号:
    7473113
  • 财政年份:
    2006
  • 资助金额:
    $ 67.96万
  • 项目类别:
QTL mapping for genes regulating apoptosis capacity
调控细胞凋亡能力基因的QTL定位
  • 批准号:
    7664549
  • 财政年份:
    2006
  • 资助金额:
    $ 67.96万
  • 项目类别:
Interaction of PTEN and CDKN1B in Pca susceptibility
PTEN 和 CDKN1B 在 Pca 易感性中的相互作用
  • 批准号:
    6954721
  • 财政年份:
    2004
  • 资助金额:
    $ 67.96万
  • 项目类别:

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