Are p53 Mutations Associated With Increased Risk of Developing Breast Cancer? A Molecular Epidermiological Study
Abstract
In a case-control study, nested within a cohort of 4,888 women with BBD, we demonstrated that p53 protein accumulation detected by immunohistochemistry was associated with a 2.5-fold increase in the risk of subsequent breast. However, by using immunohistochemistry alone, we may have underestimated the true risk of developing breast cancer. We hypothesized that p53 mutations in benign breast tissue are associated with increased risk of subsequent breast cancer. We are testing our hypothesis by: (1) analyzing benign breast tissue from 138 cases and 556 controls for the presence of p53 mutations using PCR-SSCP and PCR-direct DNA sequencing; and 2) estimating the risk of breast cancer in relation to: (a) the presence of p53 mutations in BBD; and (b) the presence of both p53 mutations and p53 protein accumulation in BBD. We also propose to compare mutations detected in the cancers with those detected in their preceeding benign breast tissue samples. In the first year of the grant, we have established the conditions for the PCR-SSCP for exons 2 to 11. 126 subjects have had sections cut, epithelium enriched tissue microdissected out, and DNA extracted. The DNA has undergone PCR-SSCP under two conditions and those with abnormal gel patterns have undergone repeat PCR-SSCP. Abnormal migrating bands have been cut from the gel .These will be sequenced. We have determined that manual sequencing rather than automated sequencing is more appropriate to analyze the p53 gene in these small paraffin embedded benign lesions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA387674
Entities
People
- Rita A. Kandel
Organizations
- Mount Sinai Hospital, Toronto