Researchers Identify Genetic Subtypes Linked to Increased Risk of Ovarian Cancer

10-year Roswell Park study shows HLA status can impact ovarian cancer risk, response to therapy

BUFFALO, N.Y. — Researchers in the Center for Immunotherapy at Roswell Park Comprehensive Cancer Center have evaluated the human leukocyte antigen (HLA), a group of genes that help regulate the body’s immune system, for underlying differences in ovarian cancer patients’ response to therapy. The scientists report that women with certain types of HLA may have an increased risk of ovarian cancer and may also respond better to immunotherapy. The research was recently published online ahead of print in the journal Gynecologic Oncology.

“Epithelial ovarian cancer is the most lethal gynecologic malignancy, with greater than 75% of patients succumbing to their disease within 5 years of diagnosis,” says Kunle Odunsi, MD, PhD, FRCOG, FACOG, senior author of the study, who is Deputy Director, M. Steven Piver Professor and Chair of the Department of Gynecologic Oncology and Executive Director of the Center of Immunotherapy at Roswell Park. “Immunotherapy has emerged as a promising and powerful tool in the fight against ovarian cancer. This research offers important insights into how to understand and employ the immune system to more effectively fight this disease.”

Researchers identified 126 patients at Roswell Park who underwent HLA testing to determine their eligibility for several clinical trials between January 2002 and December 2012. This study was designed to determine whether HLA subtypes differ between ovarian cancer patients with or without spontaneous immune response to NY-ESO-1, a protein expressed in cancers but not in normal tissue. The two major findings were that patients with the B27 HLA subtype were more likely than the general population to be diagnosed with ovarian cancer and that the B44 subtype had a worse prognosis.

“The clinical significance of an association between specific HLA subtypes and the risk of developing ovarian cancer cannot be overstated, as this may represent a new population of patients at risk for the disease. Larger studies are needed to evaluate the potential impact of these results,” adds the study’s lead author, J. Brian Szender, MD, MPH, Department of Gynecologic Oncology at Roswell Park.

This work was supported by awards from the Cancer Research Institute/Ludwig Institute for Cancer Research, including a Vaccine Collaborative Grant for Immunological Monitoring, an Ovarian Cancer Working Group grant, and an Anna-Maria Kellen Clinical Investigator award. Additional support came from the Ovarian Cancer Research Fund and National Institutes of Health grants R01CA158318-01A1, K01LMO12100, T32CA108456, P30CA016056 and the Roswell Park-UPCI Ovarian Cancer SPORE, project no. P50CA159981-01A1. The study, “HLA superfamily assignment is a predictor of immune response to cancer testis antigens and survival in ovarian cancer,” is available at ScienceDirect


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