Regina M. Santella, PhD

2012-2013 BCRF Project(s):
(made possible by generous support from Aveda)
Co-Investigator: Mary Beth Terry, PhD, Columbia University Mailman School of Public Health, New York

Drs. Santella and Terry have been studying the efficiency of repair of different types of DNA damage and have 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. In addition to biomarkers of DNA repair, these researchers have been studying DNA methylation levels as a potential biomarker of breast cancer risk in high-risk families. They are able to investigate these same biomarkers in adult women and children to understand better when breast cancer susceptibility begins. Their latest work, which they are now following up on prospectively, suggests that selected markers of DNA methylation are different in sisters with breast cancer than in sisters without cancer as well as different in young girls from cancer families compared to young girls without cancer in their families.

Working with the Breast Cancer Family Registry, which was established by the National Cancer Institute in 1995 and now totals 55,000 women and men from 14,000 families, Drs. Santella and Terry will expand their studies to a nested case-control study within the New York site of the Breast Cancer Family Registry. They will continue to measure oxidative stress markers in the young girls with and without a family history of breast cancer. There are 100 participants in the study who developed breast cancer and they will be matched by age and ethnicity to 200 individuals in the study who did not develop breast cancer.

Also, as there have been no studies of blood cell miRNAs in breast cancer, Drs. Santella and Terry will carry out a pilot study in 20 cases who donated blood within one year prior to diagnosis and 20 age- and ethnicity-matched controls. RNA will be isolated from mononuclear cells and miRs sequenced using Illumina MiSeq technology.

Mid-year Progress: Drs. Santella and Terry have evaluated expression of a panel of DNA repair genes in blood cells from breast cancer cases and controls. Women with decreased expression of several repair genes were at increased risk of breast cancer. In addition to DNA repair, this team is also examining how other biomarkers including markers of DNA methylation and oxidative stress help predict risk within families. They are able to examine the same biomarkers across generations to specifically test whether biomarkers associated with cancer risk are elevated in girls from cancer families early in life. Ultimately, their work aims at improving risk prediction and modification.

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.