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
• 负责人: Laura Fejerman
• 金额: $ 12.74万
• 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/8337724
• 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; 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; 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; 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）：美国拉丁裔女性的乳腺癌发病率低于非裔美国和非拉丁裔白人女性，但其生存率低于非拉丁裔白人。这些差异在多大程度上归因于遗传因素与非遗传因素（环境、生殖或其他）仍不清楚。该提案的主要目标是确定拉丁裔中影响乳腺癌亚型特异性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群体和环境中的普遍性。 特别是，我们将使用来自 2,900 名美国拉丁裔样本（1,600 名病例和 1,300 名对照）的全基因组关联分析 (GWAS) 的现有数据来实现以下具体目标：(1) 识别乳腺癌亚型的常见遗传风险变异，以及 (2) 识别乳腺癌进展和乳腺癌特异性生存的常见遗传风险变异。我们还将 (3) 评估目标 1 和其他已发表的 GWAS 研究中确定的已证实或暗示性风险变异对阿根廷乳腺癌病例样本的影响，以及 (4) 评估目标 2 和其他已发表研究中确定的影响进展和生存的已证实或暗示性变异是否对阿根廷样本中的疾病进展有影响。 对于前两个目标，来自旧金山湾区乳腺癌研究、乳腺癌家族登记处和多种族队列研究的样本可获取全基因组基因型、肿瘤特征和生存信息。对于目标 3 和 4，我们将对来自美国-拉丁美洲癌症研究网络研究的 600 例阿根廷病例中的 192 个 SNP（先前已确认或暗示的变异）进行基因分型。该项目将是拉丁裔中第一个通过激素受体状态以及进展和生存进行的 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 博士在该领域已经拥有丰富的经验。她特别指出，遗传血统与来自美国和墨西哥的拉丁裔女性患乳腺癌的风险有关。她目前正在与 Elad Ziv 博士一起开展第一个拉丁裔乳腺癌 GWAS，试图找到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。该提案概述了一个详细的计划，通过加州大学旧金山分校临床和转化科学研究所 (CTSI) 的 K 学者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-Stable 博士（共同导师）以及加州大学旧金山分校内外其他高级研究人员的指导培训。这项旨在促进多样性的 K01 导师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、通过主要数据收集设计研究、获得教学经验以及撰写竞争性资助。最后，她将转型成为一名成功的独立调查员，也是为数不多的拉丁裔独立调查员之一，致力于研究该人群的癌症风险。