Hispanic BRCA Mutations
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Non-technical introduction to the research topics: Breast cancer (BC) is the most commonly diagnosed cancer in Hispanic women, and is the leading cancer cause of death in this population. Mutations in the BRCA genes are associated with 5-10% of BC cases. The lifetime risk of developing BC in individuals with a BRCA mutation may be as high as 85%. There is little information on BRCA mutations in Hispanics. We recently reported on the frequency of BRCA mutations in a group of 110 Hispanic individuals of predominantly Mexican descent living in Southern California. Thirty-four (31%) of these individuals were found to have a BRCA mutation. A BRCA mutation common to individuals of Ashkenazi Jewish descent known as BRCA1 185delAG was detected in 4 of the 34 (3.6%) individuals. DNA from 67 of the 76 patients without a BRCA mutation was analyzed for the presence of large missing DNA segments (deletions) and a deletion of part of the BRCA1 gene was found in 3 of 67 (4.5%) individuals. All 3 individuals are of Mexican ancestry and are unrelated through at least a four-generation family tree, suggesting this mutation may be specific to this population. We have identified the DNA sequences on each side of this deletion and have determined its consequences at the protein-level. 
 
 
 
 
 
 
 
 The question(s) or central hypotheses of the research: The purpose of this project is to gather data on the frequency of BRCA mutations that are common among Hispanics in order to develop a more efficient way of providing genetic cancer risk assessment to women of Hispanic ancestry. 
 
 
 
 
 
 
 
 We hypothesize that: 1) the BRCA1 185delAG mutation is common in this population; 2) the large BRCA1 deletion mutation will be found at a high frequency among Hispanic families at high-risk for breast cancer; and 3) a test which includes several BRCA mutations that are common among the Hispanic population will be effective in detecting mutations in high-risk Hispanic families. 
 
 
 
 
 
 
 
 The general methodology: Tests for the BRCA1 185delAG, the BRCA1 large deletion and a panel of BRCA mutations common to the Hispanic population will be designed. Clinical data and DNA samples will be collected from two population-based and two high-risk clinic-based cohorts. Several groups of women who have been followed in other studies (cohorts) will be tested for the BRCA1 185delAG mutation and the BRCA1 large deletion mutation to determine the prevalence of these mutations. The high-risk clinic based cohorts will also be tested for the BRCA mutations common to the Hispanic population using the developed Hispanic BRCA mutation panel. We will also estimate the age of the large deletion mutation and determine if the mutation is specific to this population through analysis of DNA markers. 
 
 
 
 
 
 
 
 Innovative elements of the project: The unique Hispanic BRCA mutation panel that will be developed will help to greatly reduce the cost associated with testing high-risk Hispanic individuals for BRCA mutations. Possible outcomes of this study include more efficient breast cancer risk assessment for Hispanic women, which will allow them to choose the best way (increased breast cancer screening, healthier lifestyle choices, risk-reducing drugs, or surgery) to reduce the risk of advanced breast cancers. 
 
 
 
 
 
 
 
 Advocacy involvement and human issues: The data from this study will provide a foundation for the development of cost-effective interventions for ethnic and minority individuals at high-risk for breast cancer. There is a role for advocacy involvement in the translational phases to follow.