P53 in BBD and Breast Cancer Risk: A Multicenter Cohort

Project: Research project

Project Details


DESCRIPTION (provided by applicant): The p53 gene plays a pivotal role in
carcinogenesis. p53 gene changes are amongst the most commonly observed genetic
alterations in many cancers, including breast cancer. For breast cancer, there
is evidence to suggest that p53 gene changes occur relatively early in the
carcinogenic process; hence, such changes might be associated with increased
breast cancer risk. Therefore, in the nested case-control study proposed here,
we intend to estimate the risk of breast cancer in association with p53
mutations and/or p53 protein accumulation in benign breast tissue obtained from
1,005 cases and 1,615 controls prior to the occurrence of breast cancer (for
the cases) and at a comparable time (for the controls). Our work will be
undertaken in a large, multi-center cohort of 25,843 women who were biopsied
for benign breast disease and who have been followed-up to determine the
subsequent occurrence of breast cancer. The cohort will be created by combining
similar cohorts in Toronto, Canada (4,888 women), Portland (9,315 women),
Detroit (5,146 women), and London, England (6,494 women). p53 protein
accumulation will be detected immunohistochemically and p53 mutations will be
detected using the p53 GeneChip, with manual direct sequencing for exon 4.
Breast cancer risk in association with p53 changes will be estimated using
conditional logistic regression. For a sample of cases, p53 changes in the
benign tissue will be compared with those in the corresponding cancer tissue.
Collections of archival paraffin blocks of benign breast tissue with associated
clinical, epidemiological, and outcome information are limited, and pooling of
our data and tissue samples will allow us to examine our hypotheses
expeditiously. This molecular epidemiological study has translational potential
since it may allow refinement of risk assessment models and facilitate the
development of new approaches to the detection and clinical management of women
at risk for breast cancer. Furthermore, establishment of our international,
multi-disciplinary group will create a unique forum in which to undertake not
only this study but also further investigations of the molecular pathogenesis
of breast cancer.
Effective start/end date5/1/024/30/09


  • National Cancer Institute: $762,575.00
  • National Cancer Institute: $729,783.00
  • National Cancer Institute: $816,422.00
  • National Cancer Institute: $759,331.00
  • National Cancer Institute: $757,685.00


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