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）：美国的拉丁裔女性乳腺癌发病率低于非裔美国人和非拉丁裔白人女性，但其生存率低于非拉丁裔白人女性。这些差异在多大程度上是由遗传因素与非遗传因素（环境因素、生殖因素或其他因素）造成的，目前尚不清楚。本提案的主要目标是确定影响拉丁裔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族群和环境中的普遍性。