Breast Cancer is the result of a complex, multi-stage process in which family history, age, estrogen metabolism, tobacco smoke, and alcohol consumption comprise important risk factors. Recent studies from the laboratory of Dr. Smith-Warner and colleagues at the Harvard School of Public Health have confirmed the significant association between alcohol consumption and breast cancer that has long been suspected.
The mechanism by which alcohol consumption can increase the risk for breast cancer has not been identified previously. Breast cancer is associated with high levels of mutation and damage to DNA, as is excessive alcohol consumption. Furthermore, the genes for breast cancer have all been discovered because they are mutated forms of the natural genes. Thus all breast cancer is ultimately a disease of genes and mutations.
As alcohol is broken down in the body's cells, toxic derivatives of oxygen called oxidants of reactive oxygen species (ROS) are produced. Oxidants play an important role in breast cancer and alcohol risk because the ROS formed can cause DNA damage and mutation. Recent investigations have suggested a mechanism by which alcohol can produce the DNA damage and mutations found in breast cancer. Webb-Waring investigators have found that breast tissues contain large amounts of the enzymes that degrade alcohol, specifically alcohol dehydrogenase and xanthine oxidase. This process forms several by-products, most importantly hydrogen peroxide, that can subsequently modify and damage DNA.
Several additional factors have been discovered that influence the effect of alcohol consumption on breast cancer. For example, breast cancer strikes women more frequently after the fourth decade, and coincidentally, the levels of the protective antioxidant enzyme, catalase, that removes hydrogen peroxide, also decline with increasing age. Thus, as alcohol is degraded and hydrogen peroxide is produced, the enzyme that originally protects cells is reduced, and the hydrogen peroxide generated can then become available to subsequent reactions that damage and mutate DNA.
Additionally, iron can convert hydrogen peroxide into the primary oxidant that causes damage to DNA. For reasons not fully understood, iron accumulates in breast and other tissues as a function of age. Males and females reveal progressive iron accumulation with age that is especially enhanced in post-menopausal women whose incidence of breast cancer is highest. Importantly, blood and breast iron levels are increased in breast cancer and have been directly linked to breast cancer development through the production of oxidants. Thus, iron status should be evaluated as an important prognostic test for the increased risk of several diseases, including breast cancer.
While the role of oxidants in breast cancer is still being defined, the amelioration of several cancers, including breast cancer, by antioxidants underscores the importance of oxidants in breast cancer. The realization that oxidants may participate in the development of breast cancer suggests that antioxidants, reduction of iron intake, and reduced alcohol consumption by women in the higher age categories could significantly modulate the incidence of breast cancer.
