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
• 负责人: Laura Fejerman
• 金额: $ 12.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/8509627
• 关键词: Accounting; Address; Affect; African American; Alleles; American; Area; Argentina; Automobile Driving; Biological; Biomedical Research; Biometry; Brazil; Breast Cancer Treatment; Cancer Etiology; Cancer Research Network; Cancer Research Project; Cessation of life; Characteristics; Chile; Clinical Research; Clinical Sciences; Cohort Studies; Country; Data; Data Analyses; Data Collection; Diagnostic Neoplasm Staging; Dietary Factors; Disease Progression; Educational process of instructing; Environment; Environmental Risk Factor; Epidemiology; Estrogen Receptor Status; Estrogen receptor negative; Ethnic group; European; Exposure to; Future; Genes; Genetic; Genetic Research; Genetic Risk; Genotype; Goals; Grant; Heterogeneity; Hormone Receptor; Incidence; Institutes; K-Series Research Career Programs; Latin America; Latina; Latino; Life Style; Malignant Neoplasms; Mammary Neoplasms; Mentors; Mexican; Mexico; Minority; Molecular Profiling; NCI Scholars Program; Neoplasm Metastasis; Outcome; Pathway interactions; Pattern; Phase; Population; Prevalence; Progesterone Receptor Status; Publishing; Recruitment Activity; Research; Research Design; Research Personnel; Risk; Risk Factors; Role; Sampling; San Francisco; Scientist; Single Nucleotide Polymorphism; Stage at Diagnosis; Staging; Survival Analysis; Survival Rate; Testing; Training; Translational Research; Tumor Subtype; Uruguay; Variant; Woman; Work; Writing; anticancer research; breast cancer family registry; cancer genetics; cancer recurrence; cancer risk; clinical risk; experience; genetic epidemiology; genetic risk factor; genetic variant; genome wide association study; genome-wide; lifestyle factors; malignant breast neoplasm; mortality; non-genetic; novel; programs; reproductive; research study; risk variant; skills; tumor; tumor progression

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.

描述(申请人提供)：在美国，拉美裔女性的乳腺癌发病率低于非洲裔美国人和非拉美裔白人女性，但她们的存活率低于非拉美裔白人。这些差异在多大程度上是由于遗传因素和非遗传因素(环境、生殖或其他)造成的，目前尚不清楚。这项提案的主要目标是确定拉丁裔中影响乳腺癌亚型特定风险和进展的常见遗传风险变异，并解决这些风险因素在不同拉丁裔种族和环境中的普遍性。 特别是，我们将使用来自全基因组关联分析(Gwas)的现有数据，对2900名美国拉丁裔患者(1,600名病例和1,300名对照)进行样本分析，以解决以下具体目标：(1)确定乳腺癌亚型的常见遗传风险变量，以及(2)确定乳腺癌进展和乳腺癌特定生存率的常见遗传风险变量。我们还将(3)评估在AIM 1和其他已发表的GWAS研究中确定的风险变量在阿根廷乳腺癌病例样本中的效果，以及(4)评估在AIM 2和其他已发表的研究中确定的影响进展和生存的确认或建议变量的效果是否对阿根廷样本的疾病进展有影响。 对于前两个目标，可以从旧金山湾区乳腺癌研究、乳腺癌家族登记和多种族队列研究的样本中获得全基因组的基因型、肿瘤特征和生存信息。对于AIMS 3和AIMS 4，我们将在美国-拉丁美洲癌症研究网络研究的600例阿根廷病例中对192个SNP(先前确认或建议的变种)进行基因分型。该项目将是第一个在拉丁美洲进行的关于激素受体状态以及进展和存活率的GWAS研究。 费耶尔曼博士的目标是成为一名独立的癌症研究人员，专注于拉美裔癌症的遗传流行病学。费杰曼博士在这一领域已经有了丰富的经验。特别是，她已经证明，在美国和墨西哥的拉丁裔中，基因血统与乳腺癌风险有关。目前，她正在与Elad Ziv博士合作，在拉丁美洲开展首个乳腺癌GWAs研究，试图找到导致观察到的乳腺癌风险与基因血统之间关联的风险变量。这份提案概述了一项详细的计划，通过加州大学旧金山分校的临床和翻译科学研究所(CTSI)K-Scholars计划提供的课程来提高她在流行病学和生物统计学方面的技能。她还将接受Elad Ziv博士(首席导师)和Eliseo Perez-STRATE博士(共同导师)以及加州大学旧金山分校内外其他高级调查人员的指导培训。这项旨在促进多样性的K01指导研究科学家职业发展奖将使FeJerman博士能够获得必要的培训，以完善她在基因数据分析、进行生存分析、设计原始数据收集的研究、获得教学经验和撰写竞争性补助金方面的技能。在结论中，她将过渡到成为一名成功的独立调查员，也是为数不多的独立拉丁裔调查员之一，致力于研究这一人群的癌症风险。