The etiology of breast cancer for the most part, remains unknown. Some risk factors for breast cancer have been elucidated, which are mostly related to hormonal status or family history. Yet, these risk factors explain only a portion of the variability in disease incidence. We have been studying the role of genetic variation and gene-environment interactions for breast cancer. With our collaborators, we have focused both on hormonal and non-hormonal risk factors. We previously reported an association for smoking and breast cancer in women who had a decreased ability to detoxify tobacco smoke constituents through the NAT2 gene, as well as some weaker effects for two other genes. Among the most important findings this year, our data indicates that there is a relationship of breast cancer to genetic variation in the superoxide dismutase gene. This gene plays a role in the maintenance of reactive oxygen species in the mitochondria. By itself, the gene was predictive of breast cancer risk, and we found that the risk decreased in women who ate more foods rich in antioxidants. Thus, women have the option of modifying their susceptibility based upon their dietary behaviors. Separately, we have tested and validate the p53 sequencing methodology for the Affemetrix chip technology. More than 100 human breast cancers were sequenced by the method and by direct sequencing, with excellent concordance. We are now applying the method to several breast cancer case series. - breast cancer, Cigarette smoking, Epidemiology, Genetic Susceptibility, - Human Tissues, Fluids, Cells, etc.