Genome wide association study of breast cancer subtype and survival in Latinas

拉丁裔乳腺癌亚型与生存率的全基因组关联研究

基本信息

  • 批准号:
    8165134
  • 负责人:
  • 金额:
    $ 12.82万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-23 至 2016-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Latina women in the US have lower incidence of breast cancer than African American and non-Latina white women, but their survival rate is lower than non-Latina whites. The degree to which these differences are due to genetic vs. non-genetic factors (environmental, reproductive or other) remains unclear. The main goal of this proposal is to identify common genetic risk variants in Latinas that affect breast cancer subtype-specific risk and progression and address the generalizability of these risk factors across different Latino ethnic groups and environments. In particular, we will use existing data from a genome wide association analysis (GWAS) in a sample of 2,900 US Latinas (1,600 cases and 1,300 controls) to address the following specific aims: (1) identify common genetic risk variants for breast cancer subtypes, and (2) identify common genetic risk variants for breast cancer progression and breast cancer specific survival. We will also (3) evaluate the effect of confirmed or suggestive risk variants identified in Aim 1 and through other published GWAS studies in a sample of breast cancer cases from Argentina, and (4) evaluate if the effect of confirmed or suggestive variants that affect progression and survival identified in Aim 2 and through other published studies have an effect on disease progression in the sample from Argentina. For the first two aims, genome wide genotype, tumor characteristic and survival information is available for samples from the San Francisco Bay Area Breast Cancer Study, the Breast Cancer Family Registry and the Multiethnic Cohort Study. For aims 3 and 4 we will genotype 192 SNPs (previously confirmed or suggestive variants) in 600 Argentine cases from the US-Latin America Cancer Research Network study. This project will be the first GWAS study in Latinas by hormone receptor status and by progression and survival. Dr. Fejerman's goal is to become an independent cancer researcher focusing on genetic epidemiology of cancer in Latinos. Dr. Fejerman already has extensive experience in this field. In particular, she has shown that genetic ancestry is associated with breast cancer risk in Latinas from the US and Mexico. She is at present working, together with Dr. Elad Ziv, on the first GWAS of breast cancer in Latinas, trying to locate the risk variants that are responsible for the observed association between breast cancer risk and genetic ancestry. This proposal outlines a detailed program to advance her skill set in epidemiology and biostatistics through courses available through the Clinical and Translational Science Institute (CTSI) K-Scholars program at UCSF. She will also receive mentored training from Dr. Elad Ziv (principal mentor) and Dr. Eliseo Perez-Stable (co-mentor) and other senior investigators within and outside UCSF. This K01 Mentored Research Scientist Career Development Award to Promote Diversity will enable Dr. Fejerman to acquire the training necessary to perfect her skills in genetic data analysis, to conduct survival analysis, to design studies with primary data collection, to obtain teaching experience, and to write competitive grants. At the conclusion, she will transition to becoming a successful independent investigator, and one of the few independent Latina investigators, working on cancer risk in this population. PUBLIC HEALTH RELEVANCE: Breast cancer is the leading cause of cancer death in Latina women in the US. Latinos are the largest minority population in this country. Despite the extensive amount of cancer research performed locally and abroad, for the most part, genetic and clinical research studies of breast cancer have failed to include Latinos. This proposal is unique in its attempt to capture genetic risk factors specific for particular tumor subtypes and survival in Latinas both residing in the US and also in their countries of origin. Our findings will contribute genetic predictors of risk and clinical outcomes specific for the different known breast tumor subtypes among US Latinas. We will be able to determine if these predictors are unique for US Latinas or shared with Latinas residing outside the US. If we identify novel genetic variants that are associated with risk and survival, these variants may be in genes and biological pathways previously unrecognized. These pathways may be new targets for breast cancer treatment.
描述(由申请人提供):美国的拉丁裔妇女的乳腺癌发病率低于非裔美国人和非拉丁裔白人妇女,但其存活率低于非拉丁裔白人。这些差异是由于遗传因素与非遗传因素(环境,生殖或其他)造成的程度尚不清楚。该提案的主要目的是确定拉丁裔的常见遗传风险变异,影响乳腺癌亚型特异性风险和进展,并解决这些危险因素在不同的拉丁裔族裔群体和环境中的普遍性。 特别是,我们将在2,900种美国拉丁裔(1,600例和1,300个对照)样本中使用来自基因组广泛关联分析(GWAS)的现有数据来解决以下特定目的:(1)确定乳腺癌亚型的常见遗传风险变异,((2)确定乳腺癌进展和乳腺癌特定乳腺癌特异性的常见遗传变异。我们还将(3)评估AIM 1中确定的或暗示性风险变异的效果,以及通过来自阿根廷乳腺癌病例的样本中的其他已发表的GWAS研究,以及(4)评估是否影响AIM 2中鉴定出的确认或暗示性变异的效果,以及通过其他公开研究在AIM 2中鉴定出的进展和生存的影响,对疾病对疾病的进展产生了影响,从而在Argentina中对疾病的进展产生了影响。 对于前两个目的,可以从旧金山湾区乳腺癌研究,乳腺癌家族注册表和多种族同龄研究的样品中获得基因组广泛的基因型,肿瘤特征和生存信息。对于AIM 3和4,我们将在美国拉丁美洲癌症研究网络研究的600例阿根廷病例中基因型192 SNP(以前已确认或暗示性变体)。该项目将是激素受体状态以及进展和生存的首次在拉丁裔中进行的GWAS研究。 Fejerman博士的目标是成为一名独立的癌症研究员,专注于拉丁裔癌症的遗传流行病学。 Fejerman博士已经在这一领域拥有丰富的经验。特别是,她表明遗传血统与来自美国和墨西哥的拉丁裔乳腺癌风险有关。目前,她正在与拉丁裔乳腺癌的第一个GWAS一起工作,试图定位导致乳腺癌风险与遗传血统之间观察到的关联的风险变异。该提案概述了一项详细的计划,可以通过UCSF的临床和转化科学研究所(CTSI)K-Scholars计划获得的课程来推进她在流行病学和生物统计学方面的技能。她还将获得Elad Ziv博士(主要导师)和Eliseo Perez-Stable博士(Co-Incertor)和UCSF外部和其他高级调查员的指导培训。这项K01指导的研究科学家职业发展奖旨在促进多样性,将使Fejerman博士能够获得必要的培训,以完善她在遗传数据分析方面的技能,进行生存分析,通过主要数据收集,获得教学经验并撰写竞争力的赠款。最后,她将过渡到成为一名成功的独立研究者,并且是为数不多的独立拉丁研究人员之一,在该人群中致力于癌症风险。 公共卫生相关性:乳腺癌是美国拉丁裔妇女癌症死亡的主要原因。拉丁美洲人是该国最大的少数民族人口。尽管在当地和国外进行了大量癌症研究,但在大多数情况下,乳腺癌的遗传和临床研究仍未包括拉丁美洲人。 该提议在尝试捕获特定于特定肿瘤亚型的遗传危险因素和拉丁裔的生存方面是独一无二的。我们的发现将为美国拉丁裔中不同已知的乳腺肿瘤亚型特有的风险和临床结果的遗传预测指标。我们将能够确定这些预测因素是美国拉丁裔独特的还是与居住在美国以外的拉丁裔共享的。如果我们确定与风险和存活相关的新型遗传变异,这些变体可能在先前未被认可的基因和生物途径中。这些途径可能是乳腺癌治疗的新目标。

项目成果

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Laura Fejerman其他文献

Laura Fejerman的其他文献

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{{ truncateString('Laura Fejerman', 18)}}的其他基金

Her2 status of breast cancer in diverse populations: improving genetic prediction and understanding molecular correlates
不同人群中乳腺癌的 Her2 状况:改善遗传预测并了解分子相关性
  • 批准号:
    10660883
  • 财政年份:
    2023
  • 资助金额:
    $ 12.82万
  • 项目类别:
Biological implications of breast cancer protective variants in Latin American women with high Indigenous American ancestry
具有高美洲原住民血统的拉丁美洲女性乳腺癌保护性变异的生物学意义
  • 批准号:
    9768900
  • 财政年份:
    2016
  • 资助金额:
    $ 12.82万
  • 项目类别:
Biological implications of breast cancer protective variants in Latin Americanwomen with high Indigenous American ancestry
具有高美洲原住民血统的拉丁美洲女性乳腺癌保护性变异的生物学意义
  • 批准号:
    10216555
  • 财政年份:
    2016
  • 资助金额:
    $ 12.82万
  • 项目类别:
Biological implications of breast cancer protective variants in Latin American women with high Indigenous American ancestry
具有高美洲原住民血统的拉丁美洲女性乳腺癌保护性变异的生物学意义
  • 批准号:
    9247151
  • 财政年份:
    2016
  • 资助金额:
    $ 12.82万
  • 项目类别:
Genome wide association study of breast cancer subtype and survival in Latinas
拉丁裔乳腺癌亚型与生存率的全基因组关联研究
  • 批准号:
    8509627
  • 财政年份:
    2011
  • 资助金额:
    $ 12.82万
  • 项目类别:
Genome wide association study of breast cancer subtype and survival in Latinas
拉丁裔乳腺癌亚型与生存率的全基因组关联研究
  • 批准号:
    8337724
  • 财政年份:
    2011
  • 资助金额:
    $ 12.82万
  • 项目类别:

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