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. DNA was extracted fro the paraffin -embedded breast tissue and exons 2 to 11 of p53 were screened by PCR-SSCP followed by manual sequencing if an abnormality was detected. Manual sequencing was used as we found it detects more gene alterations than GeneChipR array. Women with an alteration in intron that is not a polymorphism and positive immunostaining for p53 have a 2.9 fold increased risk to develop breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA424156
Entities
People
- Rita A. Kandel
Organizations
- Mount Sinai Hospital, Toronto