2003 & 2006 Liz Tilberis Grant Recipient – Douglas A. Levine

Douglas A. Levine, M.D.
Memorial Sloan-Kettering Cancer Center
Method to Determine if a Male Hormone, Naturally Present in Women, Affects the Risk of Developing Ovarian Cancer

Project Summary

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.

Bio

I am a gynecologic oncologist who specializes in the surgical treatment of women with known or suspected ovarian and uterine cancers. For most women with these cancers, surgery is an important part of the initial treatment and increases the possibility of a cure. Many studies have shown that women with gynecologic cancers have better outcomes when their primary surgery is performed by a gynecologic oncologist. In addition to my expertise in the surgical management of gynecologic cancers, I also have special training in minimally invasive surgery (laparoscopy) and preventive surgery for appropriately selected patients. Intraperitoneal chemotherapy has recently been proven to be a superior method of treatment for advanced ovarian cancer, and I fully incorporate this into the treatment of appropriate patients.

When I am not caring for patients, I spend my time working in the gynecology research laboratory, where my efforts focus on the molecular genetics of hereditary and sporadic ovarian cancer. Specifically, I am trying to identify genetic risk factors that increase an individual’s likelihood of developing ovarian cancer. A major portion of this research focuses on the effect of hormones and genetic variation on the development of ovarian cancer. I am also investigating the risk of gynecologic cancer associated with BRCA mutations and the use of whole genome microarray techniques to molecularly characterize ovarian and uterine cancers. My research is supported by funding from the National Cancer Institute, the Ovarian Cancer Research Fund, the Gynecologic Cancer Foundation, and the Entertainment Industry Foundation.

In addition to caring for patients and conducting translational research, I have an active interest in medical education and innovative technology. I have authored or co-authored more than 30 peer-reviewed research papers, review articles, and book chapters. I am also the lead editor of the only full-color photographic surgical atlas in the field, Atlas of Procedures in Gynecologic Oncology. I serve on the Editorial Board of Gynecologic Oncology and am a member of the Ovarian Cancer Working Group of The Cancer Genome Atlas. My goals are to provide the highest quality comprehensive care to women with gynecologic cancers and improve patient outcomes through