Uncovering Breast Cancer Predisposition Factors in Puerto Rico

揭示波多黎各的乳腺癌易感因素

基本信息

批准号：
8551281
负责人：
Julie Dutil
金额：
$ 9.29万
依托单位：
PONCE SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8551281
关键词：
Accounting Adverse effects BRCA1 gene BRCA2 gene Biochemistry CHEK2 gene Cancer Center Cancer Research Project Candidate Disease Gene Cardiovascular Diseases Caucasians Caucasoid Race Cell Cycle Regulation Cells Collaborations Communities Coupled Custom DNA Damage DNA Repair DNA Repair Disorder DNA Repair Pathway Data Defect Development Epithelial Cells FOLH1 gene Family Fostering Foundations General Population Genes Genetic Genetic Predisposition to Disease Germ Lines Germ-Line Mutation Goals High Risk Woman Hispanics Human Genetics Individual Inherited Knowledge Left Libraries Link Malignant Neoplasms Mammary gland Mediating Medical Medicine Mentors Methods Mutate Mutation Pathway interactions Patients Physicians Play Population Positioning Attribute Predisposition Preparation Prevalence Proteins Puerto Rican Puerto Rico Regimen Research Research Infrastructure Research Personnel Research Project Grants Risk Role Sampling Signal Transduction Solid Somatic Mutation Surveys Susceptibility Gene TP53 gene Technology Testing Therapeutic Time Translational Research Treatment Efficacy Tumor Suppressor Proteins Vision Woman base cancer prevention cancer risk cancer therapy career development chemotherapy design exome experience genetic variant high risk improved inhibitor/antagonist interest investigator training malignant breast neoplasm medical schools multidisciplinary neoplastic cell programs response screening symposium tumor tumor progression tumorigenesis

项目摘要

ABSTRACT: The DNA repair pathways and the signaling networks that link DNA repair to cell cycle regulation, known as the DNA damage response (DDR), constitute a central mechanism in the development of cancer. The genes underlying DNA repair and DDR have been shown to be key players in genetic predisposition to breast cancer and subsequent tumor progression. The overall objective of the research described in this proposal is to identify the germline and somatic genetic changes in DNA damage response genes that underlie the risk of breast cancer, specifically in the population of Puerto Rico. The overall hypothesis is that the germ-line and tumor genetic factors underlying breast cancer susceptibility in Puerto Rico may differ qualitatively or quantitatively from those in Caucasian women. In specific aim #1, we will determine the prevalence of germline changes in the genes involved in breast cancer risk. We will perform a comprehensive screening of a panel 21 candidate genes that have been implicated in breast cancer predisposition in the general population. Several of those genes are involved in the cellular response to DNA damage. We will accomplish this aim using capture technology coupled with massively parallel sequencing. We expect to determine whether the genes that were previously implicated in breast cancer predisposition are also determinants of breast cancer risk in the Puerto Rican population. In specific aim #2, we propose to determine the prevalence of somatic changes in genes involved in DNA repair and DDR. This will be accomplished by the library preparation from tumor samples and full exome capture hybridization followed by massively parallel sequencing. The identification of somatic changes in DNA repair and DDR genes is expected to reveal key genes that are mutated in tumorigenesis in the Puerto Rican population. This project proposes to examine both germline and somatic changes, thereby providing an integrated picture of the role of genetic variants in DNA repair and DDR genes in breast cancer risk and development. It targets a Hispanic population, which is often underrepresented in genetic studies. Our findings may uncover genetic changes specific to this population that will allow for the development of custom-designed predisposition tests. Importantly, these data will serve the basis for a vision of personalized medicine that takes into account natural differences in populations to maximize the identification of individuals at risk and the efficacy of therapeutic regimens. This project supports the overall U54 application by fostering the close collaboration between PSM and MCC investigators while gathering knowledge that will directly improve cancer prevention and treatment in Puerto Rico.