The goals of this proposal are to (1) develop procedural and analytic methodology for, and (2) conduct initial specimen collection towards the creation of an international repository of breast tumor specimens representative of populations at widely varying risk of breast cancer. The repository will form the basis for innovative molecular epidemiologic research aimed at identifying previously unrecognized etiologies of breast cancer and at explaining the 10-fold differences in breast cancer incidence throughout the world. Uncertainty regarding the impact of environmental exposures on risk of breast cancer provides a strong incentive to develop and use biomarkers of exposure in molecular epidemiologic studies of this disease. For example, we hypothesize that characterizing differences between populations in the types of p53 mutations present in breast cancers may provide new clues to breast carcinogenesis. Differences in mutation patterns between populations may identify regions with substantial exposure to unique or currently unrecognized causes of breast cancer. Also, the specific types of mutations identified will stimulate laboratory research aimed at identifying the exposures likely to cause these mutations. We have identified a worldwide network of well-qualified investigators willing to collaborate in breast cancer research, providing a strong foundation for the development of an international breast tumor repository. Through this proposal, we will develop protocols for tissues and data to be included in the repository. Tissue and related clinical and epidemiological data from women with breast cancer will be collected in 3 study sites as a basis for initial pilot studies. The repository will be expanded after this funding period to include a larger number of populations. In addition to the examination of population differences in the mutational spectrum of p53 in breast cancers, the repository will enable a variety of other future molecular epidemiologic studies of this disease.
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