Biography

Dr. Figueroa received her Ph.D. in molecular genetics and microbiology from Stony Brook University in 2004, and an M.P.H. from the Mailman School of Public Health, Columbia University in 2005. Dr. Figueroa joined NCI in 2004 as a NCI Cancer Prevention Fellow and became an Investigator in HREB in 2008. Her research focuses on delineating the biologic mechanisms of cancer etiology in molecular epidemiologic studies, with an emphasis on breast and bladder cancers. Dr. Figueroa’s work has earned her numerous awards. Her research has been recognized at NIH by a Fellows Award for Research Excellence (FARE), a NCI Cancer Prevention Research Training Merit Award, a NCI Director’s Career Development Intramural Innovation Award, and two DCEG Intramural Research Awards, as well as by the broader research community including a Keystone Symposium Scholarship for a meeting on Genome Stability and DNA repair.

Research Interests

We are conducting molecular epidemiology studies with a special emphasis on combining multiple biomarker data in order to study the underlying biological mechanisms for breast and bladder cancer etiology. My current research focuses on evaluating known etiological pathways as well as novel pathways emerging from genetic association studies using intermediate biomarkers and tissue makers; determining the association of proven or suspected hormonally-related risk factors with molecular markers in normal breast tissue; and developing and applying novel biomarkers of susceptibility and cancer progression.

Etiological pathways of Breast Cancer

We are conducting a variety of projects evaluating known and emerging etiological pathways of breast cancer. For example, exposures that increase cumulative exposure to estrogens have been associated with increased circulating levels, and breast cancer risk; however, only a fraction of women with this risk factor profile develop clinical cancer. Accordingly, both genetic variation and somatic expression of key molecules that mediate estrogenic effects may represent an important determinant of risk. ER targeted gene transcription is dependent on interactions with several well characterized coactivators and corepressors which positively and negatively regulate ER transcription. Therefore, I am leading a project along with DCEG collaborators Louise Brinton, Montserrat Garcia-Closas, and Mark Sherman, to comprehensively assess these factors in material collected in the Polish population-based breast cancer case-control study. This includes evaluating genetic variation and somatic tumor tissue expression of these factors and their relationship with tumor characteristics and survival.

In addition to estrogen, the transforming growth factor beta (TGF-?) pathway family is emerging as a critical factor in human breast biology that produces paradoxical effects. TGF-ß pathways may suppress carcinogenesis at the outset, but later contribute to tumor progression. The contextual role of the TGF-? pathway in human breast cancer has been limited to studies with small sample sizes, partial analysis of different TGF-? pathway components, and incomplete adjustment for other tumor characteristics or other important clinical features. With CCR collaborators Drs. Kathy Flanders and Lalage Wakefield, we are evaluating tumor tissue expression of different TGF-? pathway components in order to elucidate the complex relationships between expression of TGF-? signaling factors and clinically important tumor characteristics, survival, and breast cancer risk factors in the Polish breast study.

I am also currently leading a new effort with collaborators Mark Sherman, Stephen Hewitt, and Montserrat Garcia-Closas to construct a new breast tumor tissue array as part of the Applied Molecular Pathology Laboratory for the Polish breast study in order to apply current and novel biomarkers to further our understanding of markers for susceptibility, breast cancer risk, treatment, and progression.

In addition to our tumor tissue work, we are investing in new resources to identify the relationship between molecular markers and breast cancer risk factors which remain poorly characterized. A critical balance between proliferation, differentiation, and cell death is important for normal breast development and for maintaining its physiology. Accordingly, risk factors that increase the availability of hormones, augment the proliferative response within the breast epithelium to hormones, or interfere with apoptotic responses that eliminate cells with DNA damage could be the mechanism of action for known breast cancer risk factors. A major impediment to this work has been the lack of normal breast tissue with complete epidemiologic characterization of the subjects. We are forming new collaborations with repositories that are collecting normal breast tissue along with other biospecimens in order to evaluate biomarker expression of carcinogenic pathways (such as apoptosis and proliferative responses) with established breast cancer risk factors.

Molecular Markers of Bladder Cancer Susceptibility

Bladder cancer has served as a good model for assessing genetic susceptibility and gene-environment interactions because of its relatively homogenous histology (>95% of cancers are transitional cell carcinomas), and known environmental causes (i.e., tobacco smoke and occupational exposures). Within the Spanish bladder hospital-based case control study (DCEG collaborators Debra Silverman, Nat Rothman, and Montserrat Garcia-Closas), I have employed gene-ontology methods to designate pathways of the genetic variation data, and utilized novel statistical approaches to detect gene-gene and gene-environment interactions. I have evaluated over 160 SNPs involved in base-excision and double-strand break DNA repair carcinogen metabolism, and death-receptor mediated apoptosis. Our most promising results have suggested genetic variation in the double strand break repair pathways to be potentially new markers for bladder cancer susceptibility. We are validating these findings in collaboration with the recently founded International Consortium of Bladder Cancer http://dceg.cancer.gov/icbc/. Furthermore, to follow-up on candidate and identify novel pathways associated with bladder cancer risk, we are performing a Genome Wide Association Study (GWAS) for bladder cancer, in collaboration with DCEG investigators Drs. Stephen Chanock, Nilanjan Chatterjee, Montserrat Garcia-Closas, Nathaniel Rothman and Debra Silverman. Moreover, we are evaluating functional susceptibility assays in order to assess the relationship of susceptibility genotypes and integrated assays with bladder cancer risk.

Keywords

Molecular epidemiology, molecular pathology, genetic susceptibility, breast cancer, bladder cancer

Selected Publications

• Figueroa JD, Terry MB, Gammon MD, Zhang FF, Vaughn TL, Risch HA, Kleiner D, Bennett WP, Fraumeni JF Jr., Chow WH. Tobacco, body mass, gastro-esophageal reflux disease, and non-steroidal anti-inflammatory drug use and risk of subtypes of esophageal and gastric cancers by P53 overexpression. Cancer Causes Control 2009;20(3):361-8.
• Figueroa JD, Malats N, Garcia-Closas M , Real FX, Silverman D, Kogevinas M, Chanock S, Welch R, Dosemeci M, Lan Q, Tardón A, Serra C, Carrato A, García-Closas R, Castaño-Vinyals G, Rothman N. Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes. Carcinogenesis 2008;29(10):1955-62.
• Figueroa JD, Sakoda LC, Graubard BI, Chanock S, Rubertone MV, Erickson RL, McGlynn KA. Genetic variation in hormone metabolizing genes and testicular cancer risk in STEED. Cancer Causes Control 2008;19(9):917-29.
• Landi MT, Dracheva T, Rotunno M, Figueroa JD, Shih J, Consonni D, Pesatori A, Wacholder S, Bertazzi PA, Caporaso N, Jen J. Gene expression changes by smoking in lung tumor and normal tissue from EAGLE. PLoS ONE 2008;20;3(2):e1651.
• Figueroa JD, Malats N, Rothman N, Real FX, Silverman D, Kogevinas M, Chanock S, Welch R, Dosemeci M, Lan Q, Tardón A, Serra C, Carrato A, García-Closas R, Castaño-Vinyals G, Garcia-Closas M. Evaluation of genetic variation in the double-strand break repair pathway and bladder cancer risk. Carcinogenesis 2007;28(8):1788-93

Collaborators

DCEG Collaborators

• William F. Anderson, M.D., M.P.H. Dalsu Baris, M.D., Ph.D., Louise Brinton Ph.D., M.P.H., Kenneth Cantor, Ph.D., Stephen Chanock, M.D., Nilanjan Chatterjee, Ph.D., Montserrat Garcia-Closas M.D., Dr.P.H., Qing Lan, M.D., M.P.H., Ruth Pfeiffer, Ph.D., Nathaniel Rothman, M.D., M.H.S., Mark Sherman, M.D., Debra Silverman, Sc.D., Sc.M., Rose Yang, Ph.D.

Other NCI Collaborators

• Jessica Faupel-Badger, Ph.D. M.P.H., Kathy Flanders, Ph.D., Paul Meltzer, Ph.D., Stephen Hewitt M.D., Ph.D., Lalage Wakefield, Ph.D.

Other Scientific Collaborators

• Mia Gaudet, Ph.D., Memorial Sloan-Kettering Cancer Center
• Manolis Kogevinas, M.D., Ph.D., Municipal Institute for Medical Research, Barcelona, Spain
• Jolanta Lissowska, Ph.D., M. Slodowska-Curie Memorial Cancer Center and Institute of Oncology
• Nuria Malats, M.D., Ph.D., Municipal Institute for Medical Research, Barcelona, Spain
• Beata Peplonska, M.D., Nofer Institue of Occupational Medicine, Lodz, Poland
• Paco Real, M.D., Ph.D., Municipal Institute for Medical Research, Barcelona, Spain
• David Rimm, M.D. Ph.D., Yale Medical School
• Mary Beth Terry, Ph.D., M.P.H., Columbia University