by Terry Taylor, M.A.
When asked how she got into the field of molecular epidemiology, Jonine D. Figueroa, Ph.D., M.P.H., Hormonal and Reproductive Epidemiology Branch (HREB), recalled, "I had just completed my Ph.D. in molecular genetics and cell biology, and I wanted something more applied. I heard about the NCI Cancer Prevention Fellowship Program, which allows you to get an M.P.H., and it sounded great." She was accepted into the program in 2004 and went to Columbia University for her M.P.H. She now leverages her laboratory expertise to apply molecular techniques in epidemiologic studies in order to delineate the mechanisms involved in cancer causation and progression. She hopes that this work may lead to novel strategies for risk assessment and interventions.
At NCI, she found the ideal mentor in Dr. Montserrat García-Closas, then an investigator in HREB. "With her epidemiologic and analytic expertise plus my molecular biology background, she was the perfect fit for me," Dr. Figueroa said. In 2008, Dr. Figueroa became a tenure-track investigator in the Division. Much of her initial work focused on bladder cancer as she applied her molecular background to define mechanisms of genetic susceptibility.
Dr. Figueroa later turned to breast cancer, focusing her efforts on identifying genetic and other risk markers, especially for aggressive and early-onset tumors. She recently published a pooled analysis on the association of common genetic variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and found evidence for heterogeneity by tumor subtype. These findings demonstrate the importance of conducting large studies incorporating tumor pathology data in order to provide the most robust risk models for assessing predisposition to different types of breast cancer.
In further studies, Dr. Figueroa received an NCI Director's Innovation Award to study the TP53 pathway in estrogen receptor negative (ER–) breast cancer. She explained that most identified risk factors for breast cancer are related to estrogen receptor positive tumors, which account for about 70 percent of all breast cancers. On the other hand, ER– breast cancers have been relatively understudied despite being generally more aggressive and deadly and more frequent among younger women, BRCA1 mutation carriers, and African Americans. ER– breast cancers are reported to have more TP53 mutations, the reason for Dr. Figueroa's interest in this pathway.
The theme of her current work is identifying biomarkers associated with early carcinogenic events in breast tissue. "Cancer arises at one end of the spectrum," she explained, "but we have limited understanding of the initiating events that eventually progress to breast cancers. Biomarkers are a tool we can use to help us understand the biological mechanisms by which genetic and nongenetic factors increase or decrease the subsequent risk for breast cancer."
To begin to answer this question, Dr. Figueroa is collaborating with researchers at the Susan G. Komen for the Cure Tissue Bank at Indiana University. The study population includes about 900 women volunteers, aged 18 to 83 years, who completed questionnaires and donated blood and breast tissue but who have no evidence of cancer. The goal is to look for associations between terminal ductal lobular unit (TDLU) morphology and genetic susceptibility loci as well as hormonal and other risk factors. TDLUs, which are milk-secreting structures, are thought to be where the majority of breast cancers originate.
"Are risk factors associated with changes in the TDLU structure suggesting a pathway to breast carcinogenesis? That's the question we want to answer," Dr. Figueroa explained. She and her colleagues are examining the samples of normal tissue for any sign of changing morphology, which scientists have previously shown to be an independent marker of risk in a study at the Mayo Clinic of high-risk women with benign breast disease. Tissues from the normal-tissue bank will make it possible to see whether changes occur earlier, before the onset of any disease.
"This is an exciting time to be a molecular epidemiologist because we have new technologies and population-based biological samples needed to more fully understand the molecular mechanisms leading to disease," Dr. Figueroa said.
Dr. Figueroa confesses to being a "foodie"—she regularly cooks Puerto Rican dishes with her key ingredient: sofrito. She lives with her husband Jeff, a dog geneticist, their 1½-year-old daughter Isis, and a Leonberger dog named Zeppelin. "Being a wife, mother, and tenure-track researcher is challenging," she admitted. "It has been a tough year in some ways, but I am very happy and I have fun. My motto is ‘Work Hard, Play Hard.' I think it's a good motto!"