We propose to conduct a case-control study of carcinoma in situ of the breast to be conducted in parallel with the Carolina Breast Cancer Study (CBCS). Participants will include women from the 24-county area of central and eastern North Carolina covered by the CBCS. Cases will include all women with a first diagnosis of carcinoma in situ (DCIS or LCIS) between 9/1/95 and 2/28/00 identified through the Central Cancer Registry rapid- ascertainment system developed for the CBCS. Based upon preliminary data collected during 1993, we expect 400 cases within the accrual period. Comparison subjects (controls) will consist of an equal number of women without a history of in-situ (or invasive) breast disease, frequency matched to cases based upon expected distributions by age (+/- 5 years) and race. Controls will be identified using DMV and/or HCFA records. Once a potential control has been contacted, any women who have not undergone mammography within a one year period prior to selection will be offered mammography at an institutional rate through UNC hospitals. Information on established and hypothesized risk factors for breast cancer will be obtained by personal interview using the questionnaire for the CBCS. Blood samples for extraction of germline DNA will be obtained from consenting participants, and paraffin-embedded tumor specimens and medical records will be requested for all cases. The research objectives are: (1) To identify risk factors for occurrence of DCIS and LCIS of the breast; (2) To determine whether differences in histologic appearance as well as immunohistochemical and molecular profiles of in situ lesions reflect differences in underlying etiology (i.e. exposure to specific risk factors for breast cancer); (3) To specifically evaluate the contributions of tobacco smoking and chlorinated hydrocarbon pesticides, as well as other exposures in which a study of precursor lesions is expected to have advantages over previous epidemiologic studies employing invasive breast cancer as the sole endpoint; (4) To compare cases of in-situ carcinoma in African American to Caucasian women in order to determine whether the mutational spectrum, histologic characteristics, or results of other biologic assays suggest a different (possibly more aggressive) form of breast cancer in African- American women; (5) To determine whether mutations in BRCA1, BRCA2, and other loci of inherited susceptibility represent risk factors for occurrence of in-situ carcinoma of the breast. The proposed study will benefit from utilizing the same infrastructure as the CBCS, and will involve the same group of investigators and support personnel.
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