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.
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.
|Wang, Wei; Ingles, Sue Ann; Torres-Mejía, Gabriela et al. (2014) Genetic variants and non-genetic factors predict circulating vitamin D levels in Hispanic and non-Hispanic White women: the Breast Cancer Health Disparities Study. Int J Mol Epidemiol Genet 5:31-46|
|Fejerman, Laura; Ahmadiyeh, Nasim; Hu, Donglei et al. (2014) Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25. Nat Commun 5:5260|
|Fejerman, Laura; Stern, Mariana C; Ziv, Elad et al. (2013) Genetic ancestry modifies the association between genetic risk variants and breast cancer risk among Hispanic and non-Hispanic white women. Carcinogenesis 34:1787-93|
|Pellatt, Andrew J; Wolff, Roger K; Torres-Mejia, Gabriela et al. (2013) Telomere length, telomere-related genes, and breast cancer risk: the breast cancer health disparities study. Genes Chromosomes Cancer 52:595-609|
|Fejerman, Laura; Hu, Donglei; Huntsman, Scott et al. (2013) Genetic ancestry and risk of mortality among U.S. Latinas with breast cancer. Cancer Res 73:7243-53|
|Avena, Sergio; Via, Marc; Ziv, Elad et al. (2012) Heterogeneity in genetic admixture across different regions of Argentina. PLoS One 7:e34695|
|Fejerman, Laura; Chen, Gary K; Eng, Celeste et al. (2012) Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas. Hum Mol Genet 21:1907-17|