This work is in collaboration with the UGA College of Public Health; including, Dr. Sara Wagner Robb in the Department of Epidemiology and Dr. Anne Marie Zimeri in the Department of Environmental Health. We also work closely with the UGA Lab for Environmental Analysis, led by Dr. Sayed Hassan.
Sporadic Breast Cancer: the Evasive Genetic Cause.
For more than 80% of breast cancer cases, the underlying risk each woman carried is still largely a mystery. These cases are classified as ‘sporadic’; meaning the patient had no immediate family health history of the disease. There is a major gap in our of understanding concerning the comprehensive, individual risk a woman has for developing sporadic breast cancer (BrCA). We are generally aware that exposures to certain environmental agents at specific windows of vulnerability (throughout the lifecourse) increase a woman's susceptibility to BrCA. We are looking at women's exposures to heavy metals and PCB's at key intervals or "windows" of development.
We are noting the fact these windows are not static in time, but may fluctuation, with developmental processes and vary for each individual!
For our project we define “susceptibility” as a reference to the onset of breast cancer, which is an outcome of an intermediate chronic inflammatory state that leads to tumorigeneis and is detectable as epigenetic and molecular genetic responses to exposures. Our research focuses on the question of why among women exposed to similar environments, even with similar genetic inheritance within the same family, only certain women ever develop breast cancer (BrCA). It is apparent that some women have a greater sensitivity to specific environmental agents and this translates into increased cancer susceptibility. The plasticity in risk factors suggest the biological mechanism underlying risk is modifiable, varying with and in response to environmental cues. Given that cancer is a disease of the genome, where genes and gene networks have become dysfunctional, something is likely happening to the genes during these periods of vulnerability, something modifiable, something epigenetic.
Some of our Recent Findings:
North GA has several regions of Uranium 'over exposure' and excess Lead TRIs
Epigenetic modifications, such as DNA methylation, are a mechanistic link between biological outcomes and a myriad of external environmental exposures; including, toxins, heavy metals, nutrition and stress. A clear example of this link is the observation of lifelong susceptibilities to common complex diseases, such as cancer, through altered gene regulation to tumor suppressors (i.e. hyper-methylation of BRCA1) after over-exposure to genotoxic environmental agents (i.e. cigarette smoke). We hypothesize that a notable amount of sporadic breast cancer (BrCA) case susceptibility is attributable to pro-inflammatory reactions, directed by epigenetic gene responses to heavy metal exposure at key windows of vulnerability implicit to breast development and postnatal morphogenesis. We will therefore conduct experiments that investigate how BrCA incidence is mechanistically linked to certain types and concentrations of heavy metal exposures through DNA methylation modifications of inflammatory genes.
We will also partner with existing outreach programs, building upon an asset in our community, to educate women in our area about heavy metal exposures, inflammation and sporadic breast cancer risks. We have coined our research and dissemination team, “North Georgia EPICS” (Epigenetic Portals into Inflammation-based Cancer Susceptibility).