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)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA180008-02
Application #
8723786
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Mietz, Judy
Project Start
2013-09-01
Project End
2015-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
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
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Kim, Yeong C; Zhao, Linli; Zhang, Hanwen et al. (2016) Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients. Oncotarget 7:9600-12
Cui, Jian; Luo, Jiangtao; Kim, Yeong C et al. (2016) Differences of Variable Number Tandem Repeats in XRCC5 Promoter Are Associated with Increased or Decreased Risk of Breast Cancer in BRCA Gene Mutation Carriers. Front Oncol 6:92
Lynch, Henry; Synder, Carrie; Wang, San Ming (2015) Considerations for comprehensive assessment of genetic predisposition in familial breast cancer. Breast J 21:67-75
Downs, Bradley; Kim, Yeong C; Xiao, Fengxia et al. (2015) Two PALB2 germline mutations found in both BRCA1+ and BRCAx familial breast cancer. Breast Cancer Res Treat 151:219-24
Downs, Bradley; Wang, San Ming (2015) Epigenetic changes in BRCA1-mutated familial breast cancer. Cancer Genet 208:237-40
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
COMPLEXO; Southey, Melissa C; Park, Daniel J et al. (2013) COMPLEXO: identifying the missing heritability of breast cancer via next generation collaboration. Breast Cancer Res 15:402
Xiao, Fengxia; Kim, Yeong C; Wen, Hongxiu et al. (2013) The genome of polymorphonuclear neutrophils maintains normal coding sequences. PLoS One 8:e78685