A cohort study of p53 mutations and protein accumulation in benign breast tissue and subsequent breast cancer risk

Geoffrey C. Kabat, Rita A. Kandel, Andrew G. Glass, Joan G. Jones, Neal Olson, Catherine Duggan, Mindy S. Ginsberg, Abdissa Negassa, Thomas E. Rohan

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number970804
JournalJournal of Oncology
DOIs
StatePublished - 2011

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Breast
Cohort Studies
Breast Neoplasms
Breast Diseases
Confidence Intervals
Proteins
Odds Ratio
Missense Mutation
Tumor Suppressor Genes
Case-Control Studies
Carcinogenesis
Nucleotides
Logistic Models
Mutation
Mutation Accumulation

ASJC Scopus subject areas

  • Oncology

Cite this

A cohort study of p53 mutations and protein accumulation in benign breast tissue and subsequent breast cancer risk. / Kabat, Geoffrey C.; Kandel, Rita A.; Glass, Andrew G.; Jones, Joan G.; Olson, Neal; Duggan, Catherine; Ginsberg, Mindy S.; Negassa, Abdissa; Rohan, Thomas E.

In: Journal of Oncology, 2011.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Duggan, Catherine

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