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Molecular Epidemiology of Breast Cancer; Development and Validation of Acetylation Methods for Carcinogen-DNA Adduct Detection

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Annual rept. 30 Sep 1999-29 Sep 2000

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Molecular epidemiology can elucidate new breast cancer risk factors and gene environment interactions relating to both hormonal and non-hormonal carcinogenic mechanisms. Corroborative epidemiological studies of intermediate biomarkers of carcinogenesis and laboratory studies demonstrating functional importance of the epidemiology findings are needed. The study of carcinogen-DNA adducts can provide corroborative evidence for the importance of genetic susceptibilities in breast cancer risk. We are establishing new assays for the detection of carcinogen-DNA adducts, use it for the first time in humans, and rigorously validate it to prove its utility for human breast tissue analysis in epidemiological studies, and determine adduct levels in relation to metabolizing gene polymorphisms. The assays are novel because one uses a new chemical postlabeling method and quantitates adducts by accelerator mass spectroscopy an ultrasensitive C14 detection unit. The second uses capillary HPLC and laser-induced florescence. Once validated, we will learn the variability for DNA adduct levels in the population as it relates to age, gender, race, and smoking in breast tissues from 235 donors 200 women, 35 men. We also will develop breast strains from normal donors, determine in vitro adduct formation levels and correlate these levels with p53 induction. Thus, this study will provide new information about genotype-phenotype relationships.

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  • Biochemistry
  • Medicine and Medical Research

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