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Are p53 Mutations Associated With Increased Risk of Developing Breast Cancer? A Molecular Epidermiological Study

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Annual rept. 1 Sep 2001-1 Sep 2002

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In a case-control study, nested within a cohort of 4,888 women with BED, 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 BED and b the presence of both p53 mutations and p53 protein accumulation in BED. We also propose to compare mutations detected in the cancers with those detected in their preceeding benign breast tissue samples. In the second year of the grant, we have continued the analysis of the p53 gene in DNA extracted from paraffin-embedded breast tissue. Tissue sections were cut from paraffin blocks, epithelium enriched tissue microdissected out, and DNA extracted. The DNA has undergone PCR-SSCP under two conditions for exons 2 to I land those with abnormal gel patterns have undergone repeat PCR-SSCP. Abnormal migrating bands have been cut from the gel. These are being sequenced. We have determined that manual sequencing rather than automated sequencing is more appropriate to analyze the p53 gene in these small benign lesions in the paraffin embedded tissue. MAY is more sensitive than the p53 gene chip in detecting gene alterations.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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