Genetic Abnormalities in Breast Cancer Tumors and Relationships to environmental and Genetic Risk Factors Using Twins

Abstract

Activities included 1) acquisition of archived tissue blocks on breast cancer concordant twin pairs (205 Mz and 129 DZ) and discordant pairs (550 Mz); 2) immunohistochemistry to detect the level of expression of' biomarkers (p53, HER-2/neu, ER, and PR) in the tumor tissue; 3) DNA sequencing of the p53 gene; 4) FISH to detect amplification of HER-2/neu; and 5) analysis of the association of environmental and genetic factors with the development of these markers. Blocks from 488 twins (254 in concordant pairs and 234 in discordant pairs) have been received. Based on 46 concordant pairs, intra-pair analyses showed that ER was the biomarker most likely to be identical within the pair (Kappa=O.43) and HER-2/neu was the least likely (Kappa=-0.07). The low agreement suggests that environmental factors are likely to play a role in the development of some of these tumor markers. DNA sequencing of the p53 gene has been completed for 67 cases, with 16 having at least one mutation. FISH has been completed on 81 cases. The FISH results were in high agreement with the HER-2/neu IHC results; however the p53 mutation results were not correlated with the p53 IHC results. Analysis of risk factors showed that late menarche and smoking were associated with the development on an ER+ or PR+ tumor; whereas OC use was protective.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 1999
Accession Number
ADA389338

Entities

People

  • Thomas M. Mack

Organizations

  • University of Southern California

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cells
  • Chemistry
  • Dna Sequence Analysis
  • Genetics
  • Health Services
  • Medical Personnel
  • Neoplasms
  • Proteins

Readers

  • Oncology and Biomarker-Based Cancer Detection.
  • Women's Health and Cancer Risk Research: African American Women and Pregnancy Outcomes.

Technology Areas

  • Biotechnology