Ovarian cancer is the leading cause of death from gynecologic malignancies. Over the past decade much has been learned about the causes of hereditary ovarian cancer, but little is known regarding the genetic risk factors for sporadic or non-hereditary ovarian cancer. Inherited mutations in two genes, BRCA1 and BRCA2, are responsible for approximately 10 percent of all ovarian cancer. Although women with a mutation in one of these genes represent a small fraction of all ovarian cancer cases, having either mutation gives a woman a 40 percent lifetime risk of developing ovarian cancer. Unfortunately, clinicians cannot predict which women with the mutation will develop ovarian cancer and who will remain unaffected. One of the goals of this proposal is to help predict which women with inherited mutations are most likely to develop ovarian cancer. For the women who develop sporadic ovarian cancer, predisposing genetic factors have not been identified. Evidence, though, suggests a relationship between androgens, male hormones that women also have, and ovarian cancer development. This proposal will study whether the aromatase enzyme, a key regulator of androgen levels, serves as a risk modifier for ovarian cancer in general and among women with hereditary disease. The approach will capitalize on characterizing haplotype blocks, or regions of the human genome that may be linked to a disease. The findings should aid in risk stratification and targeting individuals for therapeutic interventions to reduce the overall burden of ovarian cancer.
Director, Gynecologic Oncology
Head, Gynecology Research Laboratory
Professor, Division of Gynecologic Oncology
Laura and Isaac Perlmutter Cancer Center
New York University Langone Health
Douglas A. Levine MD is gynecologic oncologist who specializes in the surgical treatment of women with known or suspected ovarian or uterine cancers.
In addition to his clinical practice, Dr. Levine is the current Head of the Gynecology Research Laboratory, where he studies cancer prevention, precision medicine, and rare tumors with unmet needs. He serves as the translational scientist on many national clinical trials determining what genomic alterations are associated with response to targeted therapies. He discovered universal mutations in SMARCA4 that drive small cell carcinoma of the ovary, hypercalcemic type. Dr. Levine has an outstanding level of expertise and leadership in ovarian and endometrial cancer research and a deep commitment to women’s health.
Dr. Levine has been very active within the NIH-sponsored Cancer Genome Atlas project (TCGA). He served as co-chair of the ovarian, endometrial, uterine carcinosarcoma, and Pan-GYN disease working groups. He is a member of the Scientific Advisory Committee of the Ovarian Cancer Research Alliance, Clearity Foundation, and Honorable Tina Brozman Foundation. He has authored or co-authored more than 220 peer-reviewed articles and two textbooks. Dr. Levine has received funding from the National Cancer Institute, the Department of Defense, Stand Up 2 Cancer, and the Gynecologic Oncology Group. He has been awarded the American Congress of Obstetricians and Gynecologists Mentor Award, served as co-chair of the American Association for Cancer Research Special Conferences on Ovarian and Endometrial Cancers, received the Foundation for Women's Cancer Excellence in Ovarian Cancer Research Prize, is the Assistant Dean of the Department of Defense Ovarian Cancer Academy, the translational science co-chair of the NRG Oncology Corpus Committee, a member of the NCI Cancer Prevention Steering Committee, and Chair of the NCI Cancer Biomarkers Study Section.