Obesity is modifiable risk factor for ovarian cancer, study finds

March 31, 2014

Ovarian cancer tumors in obese mice grew to nearly three times the size of tumors in non-obese mice, researchers discovered in a recent study. Their findings, published in the April issue of the journal Gynecologic Oncology, revealed insight into the reasons why.

Dr. Liza Makowski

Dr. Liza Makowski

The research team, led by Liza Makowski, PhD, assistant professor of nutrition in UNC’s Gillings School of Global Public Health, and lead principal investigator Vickie Bae-Jump, MD, PhD, associate professor of obstetrics and gynecology in the UNC School of Medicine, used a novel genetically engineered mouse model of serous ovarian cancer to examine effects of obesity on ovarian cancer progression and to help understand risk factors that affect patient outcomes.

Previous studies have linked obesity to increased risk of many cancers, including breast, colon and endometrial cancers, and worse outcomes for ovarian cancer patients. About 1.5 million new cancer cases are diagnosed annually, nearly 1 in 5 due to obesity, leading to a half-million cancer deaths each year. Ovarian cancer is one of the most deadly forms of the disease, and studies show obesity is associated with worse outcomes for ovarian cancer patients.

“The extremely poor prognosis for ovarian cancer, combined with dramatic rising rates of obesity, add urgency to investigating whether obesity is a risk factor that, if modified, could prevent ovarian cancer,” Bae-Jump said.

Experts in the field postulate that the consumption of a high number of calories, which leads to obesity, provides a wealth of nutrients and growth factors to cancer cells, creating an ideal environment for tumors to form and grow. Chronic inflammation and immunosuppression also are thought to link obesity and cancer.

Makowski, Bae-Jump and their co-authors used a mouse model in which they had deleted tumor suppressor genes and inactivated certain proteins on the surface of the ovarian epithelial cells to drive tumor formation. Some mice were fed a diet high in fat to make them obese, while others were given low-fat food to keep them lean. After tumors formed, the researchers performed gene expression and metabolomic profiling to assess differences in the tumors in the two groups.

By that time, mice on the high-fat diet weighed twice as much as those in the low-fat diet group, and the tumors in the obese group were significantly larger than those in the non-obese cohort. Additionally, tumors in the obese mice were biologically distinct from tumors in the lean mice.

“This suggests that obesity is a risk factor that we may be able to modify,” Makowski said, “and, with further study, this could be important information to convey to patients about ovarian cancer risk.”

The metabolic consequences of obesity may be crucial to the mechanisms that cause ovarian cancer. Understanding these obesity-specific chemical pathways may lead to new treatment and disease-management strategies. 

The research team included Chunxiao Zhou, MD, and Yan Zhong, MD, of UNC Lineberger Comprehensive Cancer Center’s gynecologic oncology division; Cheng Fan, MS, also of UNC Lineberger; Pei Fen Kuan, PhD, research assistant professor of biostatistics at the Gillings School; and Megan Difurio, MD, clinical assistant professor in the UNC School of Medicine’s Department of Pathology and Laboratory Medicine.


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Gillings School of Global Public Health contact: David Pesci, director of communications, (919) 962-2600 or dpesci@unc.edu.