Oxidants and antioxidants in breast cancer

Although a number of risk factors have been identified for breast cancer, mechanisms by which they increase risk of the disease are not clear. Breast cancer etiology could, in part, be related to oxidative stress. Recognized risk factors for breast cancer include a family history of the disease. BRCA1 is needed for post-transcriptional repair of oxidative damage, indicating that oxidative stress may be an important risk factor for women with a family history of the disease. Reproductive and hormonal factors that result in greater exposure to circulating estrogens also increase risk, and steroid hormones are metabolized to reactive quinones and hydroquinones, which can directly damage DNA. Alcohol consumption is associated with increased risk, and the metabolism of alcohol results in production of DNA-damaging reactive oxygen species (ROS). Finally, the inverse relationship noted with consumption of fruits and vegetables could be related to their being a source of antioxidant vitamins. Endogenous factors may play an equally important role in the effects of oxidative stress on breast carcinogenesis. Genetic variability in enzymes that result in increased production of ROS and those that protect the cell from oxidative stress could also have an impact for risk of the disease. In this review, a rationale is given for linking breast cancer risk factors to oxidative stress. The possible role of genetic polymorphisms in a number of enzymes that may be important in affecting levels of ROS to which the cell is exposed, as well as those that protect the cell from oxidative stress, is discussed.