Breast cancer (BC) is a complex disease with both genetic and environmental causes, and is the second leading cause of cancer death in women. Most women who develop breast cancer (approximately 70%) have no known family history or obvious risk factors. The remaining 30% of cases tend to aggregate in families, and 5-7% of these are heritable through BRCA1 and BRCA2 mutations, the only gene tests currently available for breast cancer. Recent molecular studies of breast ductal epithelial cells and tumor tissue have demonstrated the presence of several DNA repair and tumor control genes whose expression into functional proteins is effectively shut down or silenced via DNA methylation. It is hypothesized that the presence of silenced tumor control genes in breast epithelial cells may presage the eventual development of BC in women with such molecular modifications.
The specific aims of this research are: 1) to identify methylation suppressed tumor control genes in DNA isolated from breast tumor tissue and surrounding healthy breast tissue in a cohort of women at high risk for BC, as compared to a case-matched control cohort of women at average risk for BC, and 2) to determine the predictive contributions of family and personal factors on breast cancer outcome, such as a history of BC, age-of-onset, parity, age at menarche, previous breast biopsies, endogenous and exogenous hormone exposure, screening history, and BRCA mutation status. This research has implications for improving risk assessment, and may ultimately aid women in the decision-making process regarding screening and risk reduction prophylactic measures such as risk reduction mastectomy and chemoprevention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NR008311-04
Application #
7119697
Study Section
National Institute of Nursing Research Initial Review Group (NRRC)
Program Officer
Hare, Martha L
Project Start
2003-09-29
Project End
2007-05-28
Budget Start
2006-09-29
Budget End
2007-05-28
Support Year
4
Fiscal Year
2006
Total Cost
$35,332
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Nursing
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Swift-Scanlan, Theresa; Vang, Russell; Blackford, Amanda et al. (2011) Methylated genes in breast cancer: associations with clinical and histopathological features in a familial breast cancer cohort. Cancer Biol Ther 11:853-65
Swift-Scanlan, Theresa; Blackford, Amanda; Argani, Pedram et al. (2006) Two-color quantitative multiplex methylation-specific PCR. Biotechniques 40:210-9