Regina M. Santella, PhD

2009-2010 BCRF Project:
(made possible by generous support from Aveda)
Co-Investigator: Mary Beth Terry, PhD, Columbia University Mailman School of Public Health, New York

The researchers at Columbia have demonstrated the importance of DNA repair capacity in breast cancer risk and that the effect of some environmental exposures is influenced by ability to repair DNA damage. They are extending this work to pathways that repair other types of DNA damage. They will use biospecimens and data from over 1,000 women, 500 of whom have breast cancer and over 500 sisters who do not have breast cancer to investigate two areas. First, they will expand their ongoing studies on the impact of a woman's ability to repair damaged DNA on her breast cancer risk. They have already demonstrated that ability to remove bulky chemicals bound to DNA and to repair double strand breaks influences risk and are currently generating data on the mismatch repair pathway. They will now genotype subjects to determine the relationship of genotype to risk and also whether it predicts phenotype. In other studies, they have data suggesting a positive association between lower levels of genomic DNA methylation and breast cancer risk and that certain risk factors impact on DNA methylation levels.

Mid-Year Progress Report:
The team at Columbia has been studying the efficiency of repair of different types of DNA damage and has now demonstrated that deficiencies in two different repair pathways impact on breast cancer risk. Risk increases with the number of pathways in which women have deficient repair capacity. Other studies are looking at changes in the normal pattern of one type of DNA modification (methylation) that controls gene expression. Initial studies suggest methylation is impacted by environmental factors and associated with risk. A recent pilot study also suggested that breast cancer risk factors may be associated with methylation in white blood cells in early life.

Bio:
Regina Santella is Professor of Environmental Health Sciences at the Mailman School of Public Health at Columbia University, and Director of the NIEHS (National Institute of Environmental Health Sciences) Center for Environmental Health in Northern Manhattan, of the Carcinogenesis Program and Biomarkers Core Facility of the Cancer Center and of the Jean Sindab African American Breast Cancer Project.

Dr. Santella's research involves the development of laboratory methods for the detection of human exposure to environmental and occupational carcinogens, and their use in molecular epidemiology studies to identify causative factors, susceptible populations, and preventive interventions. Her work has concentrated on the measurement of carcinogens bound to DNA with highly specific and sensitive immunoassays using monoclonal and polyclonal antibodies that her laboratory has developed.

Studies specifically related to breast cancer include measurement of polycyclic aromatic hydrocarbon-DNA adducts in lymphocytes of cases and controls in the Long Island Breast Cancer Study Project and the determination of polymorphisms in genes related to metabolism of estrogens and carcinogens, oxidative stress and DNA repair. Other studies are investigating DNA repair capacity using phenotyping assays. To date these studies have demonstrated elevated levels of DNA damage in women with cancer, and that DNA repair capacity is lower in women who develop cancer compared to healthy women.

Dr. Santella has a MS in Organic Chemistry from the University of Massachusetts and a PhD in Biochemistry from the City University of New York. She has served as a member of the Metabolic Pathology Study Section as well as ad hoc reviewer for the American Cancer Society and NIEHS. She is currently a Senior Editor of Cancer Research; Past Chairperson of the Molecular Epidemiology Working Group of the American Association for Cancer Research, and Chair of the Molecular Epidemiology Subcommittee of the Southwest Oncology Group.