Mary Beth Terry, PhD

Developing better risk prediction models by incorporating biomarkers of environmental exposures, genetic susceptibility, and non-genetic alterations to DNA.

Impact

Environmental chemicals such as polyaromatic hydrocarbons (PAH) and dichlorodiphenyltrichloro-ethane (DDT) cause DNA damage that can lead to cancer. The severity of the damage and the ability to repair it influences the risk for development of breast cancer. Women with an already high risk of breast cancer, due to inherited factors or strong family history, may be more vulnerable to environmental pollutant exposure. Using the data from two established registries of high-risk families, Dr. Terry and colleague Dr. Regina Santella have examined the impact of environmental exposures in young girls. Previous studies include investigating how environmental exposures and genetic susceptibility—specifically as it relates to the ability to repair DNA damage—are related to breast cancer risk. Dr. Terry and new BCRF investigator Dr. Hui Chen Wu will continue this work to develop and validate biomarkers that can be used in conjunction with current breast cancer risk assessment models to enhance screening and preventive measures for those at high risk of developing breast cancer.

Progress Thus Far

The team has shown that exposure to PAH, a common environmental pollutant, increased the risk of breast cancer in high-risk women. Using a method developed in their laboratories, they discovered that this risk is almost 3-fold greater in women whose cells were deficient in DNA repair functions i.e., those already at high genetic risk due to inherited mutations in genes such as BRCA1/2. Other studies examining 92 cancer-related proteins showed four proteins formed clusters with other metabolites and were positively associated with breast cancer risk—this suggests that profiling protein markers in blood can help identify those that play a role in breast cancer development.

What’s next

Extracellular vesicles (EVs) are particles released from cells that contain many factors including proteins, DNA, and microRNA. Found in the blood, EVs are a potential source of disease-associated biomarkers with EV-associated microRNAs (miRNAs) known to play crucial roles in numerous physiological and pathological processes including breast cancer progression. The next step of Drs. Terry and Wu’s research program focuses on understanding the role of EV-associated microRNAs and they hope to specifically identify miRNA biomarkers associated with breast cancer progression. Their comprehensive analyses could yield robust and reliable biomarkers that are critically needed to improve risk assessment, diagnostic routines, and clinical outcomes for patients with breast cancer.