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Are There Sex Differences in Cancer?

July 17, 2023
by Amanda Steffen

Pictured above: Dr. Pamela Kunz presents the first data from her WHRY study.

A cancer typically found in the gastrointestinal tract, called a neuroendocrine neoplasm (NEN), is often considered a chronic cancer because it grows more slowly in comparison to other cancers. This means patients often undergo regular monitoring and treatment for years, and consequently can have prolonged adverse effects from the treatment they receive. These adverse effects – commonly referred to as “side-effects” – reduce patient functioning and increase costs for patients and health systems.

Pamela Kunz, MD, Associate Professor of Internal Medicine (Medical Oncology) and the Director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center is focusing her WHRY study on whether there are sex and gender differences in the epidemiology, treatment-related adverse effects, and outcomes of these cancers. Dr. Kunz recently presented the results of the first of these three study aims.

Using the public National Inpatient Sample (NIS) database, Dr. Kunz evaluated hospitalized patients with NENs and found differing rates and types of symptoms reported by male and female patients. Females experienced about 1.5 times more oral toxicities, such as mouth sores or loss of taste, and more than 3.5 times more neurologic toxicities, such as headache. Within GI symptoms, female patients experienced 1.6 times more nausea and vomiting; male patients have more fluid in the abdomen and difficulty swallowing. These symptoms were reported as severe enough to require hospitalization and serve as estimates of the adverse effects of cancer treatment. Of note, although only sex was reported in the NIS database and the analysis uses the terms male and female, Dr. Kunz points to the importance of including gender and the interaction of sex and gender in future databases.

Dr. Kunz’s second investigatory aim is now underway using four completed federally-funded clinical trials of NEN treatment to examine the relationship of patients' sex with treatment effects and clinical outcomes. The third aim will focus on the biologic reasons females and males experience toxic effects from two of the most common anti-tumor therapies used to treat NENs. Dr. Kunz and her research team are studying sex differences in the tumors to identify genes or genetic variants which may explain why females experience different or more severe adverse effects than males. This information lays the groundwork for available remedies to prevent or control adverse effects and improve the lives of patients. In this study, Dr. Kunz also plans to incorporate an analysis of hormones and self-identified gender.

Her research, which was awarded the Wendy U. and Thomas C. Naratil Pioneer award in 2022, is one of the first comprehensive studies to examine the role of sex and gender in NENs with a focus on the differing ways in which patients experience the effects of treatment and have different outcomes.

Submitted by Amanda Steffen on July 03, 2023