Environmental Exposures, Genetic Polymorphisms and p53 Mutational Spectra in a Case-Control Study of Breast Cancer

摘要

The first goal report for the project. We had previously determined that the NAT2 slow acetylator genotype and cigarette smoking is a risk factor for breast cancer. In this project, we evaluated the relationship of several genetic variants and breast cancer risk. MnSOD2 was a risk factor, that was increased by diets low in antioxidants. We did not find that NAT2 and meat consumption was a risk factor. Other genetic analyses are completed for MEH3, MEH4, CYP2D6, GSTMl, GST-T and CYP1A1. We have been validating a p53 mutational spectra detection technology using the Affymetrix gene chip array. This is going well and more than 300 blocks have been received for analysis, with another 200 to be delivered. The spectra in all these blocks will be completed with additional funding from the NCI Intramural program (about 100 tumors are completed to date). To corroborate the epidemiological data, 53 breast cell strains have been established and metabolism is being studied in relation to genotypes. Methodological conditions are being addressed. We are also developing a new carcinogen-DNA adduct methodology for use in breast tissues. The preliminary data for this was supported by this grant. We also have been studying smoking behavior and addiction, where, genetic polymorphisms in dopamine receptors and the dopamine transporter gene were addiction risk factors. This project resulted in 19 publications to date.