Genetics and Family History
In addition to the two genes linked to breast cancer—BRCA1 and BRCA2—there are other genes that may be related to breast cancer causation. On top of that, environmental exposures may interact with genes to increase breast cancer risk.
When we hear about a genetic cause of a disease, we may think that means a single gene can lead directly to a specific disease. But it's not that simple. Genetic links to disease are as complicated as the environmental connections to disease. To make things even more complicated, genetic and environmental factors can interact to predispose individuals to diseases, including breast cancer.
In the mid-1990s, researchers discovered two genes linked to breast cancer—BRCA1 and BRCA2. Both of these genes can be inherited from one's parents and passed from generation to generation in much the same ways as other familial characteristics. These two genes are known as tumor-suppressor genes, which means they help repair DNA and make sure that cells in the body reproduce exact replicas, instead of cells that can turn into tumors.[1] Mutations in these cells can run in some families, and the mutated versions are less effective in their job of making sure new cells are healthy. This increases susceptibility to breast cancer, but not all individuals with these mutations develop the disease. Factors like early exposures to toxic chemicals and radiation may negatively influence these genes.[2]
Exposure to some chemicals can turn genes on or off, complicating the link between genetics and disease.
Other genes may be related to breast cancer causation, although the effects of these genes are less dramatic. Genes that manage how the body makes and breaks down hormones, as well as other genes that affect DNA repair, may also be involved. Indeed, a range of genes working in concern may affect susceptibility to breast cancer.[3]
This complexity of multiple genes working together may make some individuals more susceptible to environmental, hormonal and lifestyle factors. In addition, a newer field of research called epigenetics illustrates that complex process underlie how genes work. Epigenetic processes can essentially turn genes "on" and "off," and therefore subtly affect certain processes related to health and disease.[4] These epigenetic effects can add up over a lifetime. A number of environmental toxicants, including heavy metals, several organic solvents and endocrine-disrupting compounds, have been shown to lead to epigenetic changes in disease activity.[5]
- Oldenburg RA, Meijers-Heijboer H, Cornelisse CJ, Devilee, P (2007). Genetic susceptibility for breast cancer: how many more genes to be found? Critical Reviews in Oncology/Hematology 63:125-149.
- King MC, Marks JH, Mandell JB, New York Breast Cancer Study Group. (2003). Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302: 643-646.
- Ghoussaini M, Pharoah PDP (2009). Polygenic susceptibility to breast cancer: current state-of-the-art. Future Oncology 5:689-701.
- Dworkin AM, Huang THM, Toland AE (2009). Epigenetic alterations in the breast: implications for breast cancer detection, prognosis and treatment. Seminars in Cancer Biology 19:165-171.
- Chiam K, Tilley W, Butler L, Bianco-Miotto T (2009). The dynamic and static modification of the epigenome by hormones: A role in the developmental origin of hormone related cancers. Biochimica et Biophysica Acta 1795: 104-109.
