Our proposal addresses the PQD3 in the RFA-CA-12-022: "What underlying causal events - e.g., genetic, epigenetic, biologic, behavioral, or environmental - allow certain individuals to survive beyond the expected limits of otherwise highly lethal cancers?" BRCA1 mutation is one of the best-known genetic causes for breast cancer. In BRCA1+ families, up to 80% of the family members who inherited BRCA1 mutation will develop breast cancer by age of 70, whereas 20% of the family members who also inherited BRCA1 mutation (BRCA1+ carrier) are breast cancer-resistance in that they will never develop breast cancer in their lifetime. In this proposal, we plan to study the genetic basis of breast cancer-resistance. We plan to use exome sequencing method to compare the entire genes between the breast cancer-affected and breast cancer- unaffected pairs from the same BRCA1+ families to identify the genes mutated differently between the two types of family members and to determine their functional relevance to breast cancer. Our proposal directly addresses the PQD3 by identifying the genes that protect the BRCA1+ individuals from breast cancer.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA180008-02
Application #
8723786
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Mietz, Judy
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198
Xiao, Fengxia; Kim, Yeong C; Snyder, Carrie et al. (2014) Genome instability in blood cells of a BRCA1+ breast cancer family. BMC Cancer 14:342
Wen, Hongxiu; Kim, Yeong C; Snyder, Carrie et al. (2014) Family-specific, novel, deleterious germline variants provide a rich resource to identify genetic predispositions for BRCAx familial breast cancer. BMC Cancer 14:470