ABSTRACT
This chapter reviews known and suspected risk factors for breast cancer, and the possible modification of risk relationships by genetic variability in mechanistic pathways. The ability to link breast cancer risk factors to mechanisms of carcino-genesis can be enhanced by exploring the role of genetic polymorphisms in the various pathways related to exposure and response in affecting ultimate agents that can damage DNA. The timing of carcinogenic exposures may be critical to risk of breast cancer. In rats, carcinogens administered before a first pregnancy result in twice the tumor load than in rats exposed after mammary cell differentiation. It is possible that etiologic pathways may differ for pre- and postmenopausal breast cancer, with the effects of specific risk factors having differential effects by menopausal status. In most epidemiological studies, the presence of breast cancer in a first-degree relative is associated with an approximate twofold elevation in breast cancer.
