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Journal of Oncology
Volume 2011, Article ID 970804, 9 pages
Research Article

A Cohort Study of p53 Mutations and Protein Accumulation in Benign Breast Tissue and Subsequent Breast Cancer Risk

1Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2Department of Pathology and Laboratory Medicine, The Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5
3Center for Health Research, Kaiser Permanente Northwest, Portland, OR 97227, USA
4Department of Pathology and Laboratory Medicine, Weill-Cornell Medical Center, New York, NY 10065, USA
5Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA

Received 11 March 2011; Revised 11 April 2011; Accepted 3 May 2011

Academic Editor: J. F. Simpson

Copyright © 2011 Geoffrey C. Kabat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Mutations in the p53 tumor suppressor gene and accumulation of its protein in breast tissue are thought to play a role in breast carcinogenesis. However, few studies have prospectively investigated the association of p53 immunopositivity and/or p53 alterations in women with benign breast disease in relation to the subsequent risk of invasive breast cancer. We carried out a case-control study nested within a large cohort of women biopsied for benign breast disease in order to address this question. After exclusions, 491 breast cancer cases and 471 controls were available for analysis. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Neither p53 immunopositivity nor genetic alterations in p53 (either missense mutations or polymorphisms) was associated with altered risk of subsequent breast cancer. However, the combination of both p53 immunopositivity and any p53 nucleotide change was associated with an approximate 5-fold nonsignificant increase in risk (adjusted OR 4.79, 95% CI 0.28–82.31) but the confidence intervals were extremely wide. Our findings raise the possibility that the combination of p53 protein accumulation and the presence of genetic alterations may identify a group at increased risk of breast cancer.