) There are presently few reliable biological criteria for distinguishing women at risk for breast cancer. There is an urgent need to identify biochemical and molecular correlates of early carcinogenic events in this malignancy. Such biomarkers might reduce the costs of prevention trials and therapy by identifying women at greatest breast cancer risk who might undergo more frequent screening or more intensive clinical management. In the proposed P01 application we will obtain 20,452 blood and urine specimens from previously interviewed Japanese, Native Hawaiian, and Caucasian women with a wide range of dietary intakes and life experiences. Blood samples will be processed and stored in liquid nitrogen.0 Urine will be stored at -80 C. Our objective is to examine the association of breast cancer with prediagnostic blood and urine concentrations of phytochemicals (lignans, isoflavones and their metabolites, carotenoids, tocopherols), hormones (estrogens, androgens), and growth factors (insulin- like growth factor) with acceptable reproducibility. During the average 3 years of follow-up, we expect to identify 205 women with postmenopausal breast cancer through the Hawaii Tumor Registry. Two postmenopausal controls will be matched to each case on ethnicity, age at phlebotomy, date and time of specimen collection, time since last meal, and the use of hormone replacement therapy within the six months preceding the blood draw. We will minimize the effect of intra-individual variability through a calibration study of 150 women to correct for measurement error, and we will make certain that the reproducibility of the biological markers under investigation is acceptable. By the end of the study, we will be able to test several primary hypotheses with adequate power. In the longer-term, we will explore interactions of dietary, hormonal, genetic, and lifestyle factors that can be easily and economically measured, and that may serve as useful adjuncts to broad-based screening.
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