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Regina M. Santella, PhD
Professor of Environmental Health Sciences
Vice Dean for Faculty Affairs
Mailman School of Public Health
Co-leader Cancer Population Science Program
Herbert Irving Comprehensive Cancer Center
New York, New York
Goal: To understand the impact of environmental exposures on breast cancer risk.
Impact: Drs. Santella and Terry are conducting studies of how non-genetic changes to DNA and environmental concerns such as pollution affect the likelihood of developing breast cancer in average- and high-risk women. Their findings may lead to better risk prediction models in high-risk individuals.
What’s next: The team has previously developed a method of determining an individual’s ability to repair double strand breaks in DNA and will now develop one for repair of DNA damage related to binding of bulky carcinogens. They will also initiate investigations to determine the effect of endocrine disrupting chemicals on breast cancer risk. In addition, Drs. Santella and Terry will extend their studies to include women in West Africa with high early onset breast cancer.
When breast cancer occurs frequently in families, it can be due to both genetics and environmental factors. A person’s DNA can affect how their body responds to various environmental influences, such as diet, and chemical exposures. Drs. Santella and Terry are conducting several ongoing studies that measure these exposures and resulting non-genetic damage to DNA in order to improve breast cancer risk prediction models for high-risk families
Full Research Summary
Research area: Developing better risk prediction models in high-risk individuals by incorporating biomarkers of environmental exposures, genetic susceptibility, and non-genetic DNA alterations.
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 exposure to environmental pollutants. Drs. Santella and Terry have been investigating how environmental exposures and genetic susceptibility—specifically as it relates to the ability to repair DNA damage—are related to breast cancer risk. This work will improve risk assessment models and allow for more precise preventive interventions.
Current research: Drs. Santella and Terry are developing tests to measure different types of DNA damage in a sample of blood to study how DNA repair deficiency affects breast cancer risk among diverse populations of high-risk women.
What they’ve learned so far: In previous BCRF supported work, the team found that exposure to PAH, a common environmental pollutant, increased the risk of breast cancer in high-risk women and that deficient DNA damage repair is involved in this increased risk.
What’s next: In the coming year, Drs. Santella and Terry will develop a new assay to determine the efficiency of DNA damage repair in breast cancer patients in the Breast Cancer Family Registry (BCRF) to determine the role of DNA repair on the development of second cancers and overall mortality. They will also expand their studies to examine the levels of endocrine disrupting chemicals in the plasma of women in the BCFR and how they affect both risk and prognosis after breast cancer diagnosis. In collaboration with investigators in Ghana, they will conduct similar studies in young women with and without breast cancer.
Regina M. Santella, PhD, is a Professor of Environmental Health Sciences. She is a laboratory-based biochemist with extensive experience in the area of chemical carcinogenesis and molecular epidemiology. Her research is mainly focused on the use of biomarkers of exposure and genetic susceptibility to understand risk for cancer development. Her laboratory has developed antibodies and immunoassays to a number of carcinogen-DNA and protein adducts and uses these methods to determine exposure to environmental carcinogens. Other assays have been used to understand genetic susceptibility related to DNA repair capacity. More recently, her laboratory is investigating the use of epigenetic markers including global and gene specific methylation and microRNA expression in breast tumors and white blood cells to identify those at increased risk or as early biomarkers of disease. Breast cancer studies take advantage of two large sample banks, the Long Island Breast Cancer Study Project, a population-based case-control study and the Breast Cancer Family Registry of members of high risk families.