ID
45655
Description
Principal Investigator: San Ming Wang, MD, University of Nebraska Medical Center, NE, USA MeSH: Breast Neoplasms,Genes, BRCA1,Germ-Line Mutation https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001243 Our study addressed a specific question in NCI 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?". A germline mutation in BRCA1 (BRCA1+) is the most penetrant genetic predisposition for breast cancer. Nevertheless, a portion of BRCA1+ carriers does not develop breast cancer in their lifetime, suggesting that the genetic predisposition can be antagonized by resistant factors. BRCA1+ was inherited from an ancestor of the carrier family thousand years ago. We hypothesize that evolution could select certain genetic components to suppress oncogenesis caused by the predisposition. We compared germline variants in all genes in 27 pairs of breast cancer-unaffected and -affected BRCA1+ carriers, each pair inherited the same BRCA1+. We identified 12 deleterious variants enriched in breast cancer-unaffected carriers, all are common variants. A variant rs3735400 is located in ANLN, a cytokinesis-essential gene. Overexpression of variant-containing ANLN and suppressed expression of endogenous ANLN decrease ANLN nuclear localization and delay cell growth. Our findings suggest that common variants can be selected to resist oncogenesis imposed by BRCA1+.
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Versions (1)
- 3/21/23 3/21/23 - Simon Heim
Copyright Holder
San Ming Wang, MD, University of Nebraska Medical Center, NE, USA
Uploaded on
March 21, 2023
DOI
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License
Creative Commons BY 4.0
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dbGaP phs001243 Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier
Subject ID, affection status, and consent group of participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
- StudyEvent: SEV1
- Subject ID, affection status, and consent group of participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
- Subject ID, sample ID, and sample use variable obtained from participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
- Subject ID, age, and race of participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
- Sample ID, anlalyte type, body site where sample was obtained, disease status, and tumor status of sample obtained from participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
Similar models
Subject ID, affection status, and consent group of participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
- StudyEvent: SEV1
- Subject ID, affection status, and consent group of participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
- Subject ID, sample ID, and sample use variable obtained from participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
- Subject ID, age, and race of participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
- Sample ID, anlalyte type, body site where sample was obtained, disease status, and tumor status of sample obtained from participants with breast cancer and involved in the "Genetic Basis of Breast Cancer Resistance in BRCA1 Mutation Carrier" project.
C0441833 (UMLS CUI [1,2])
C0242481 (UMLS CUI [1,2])