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Long-term NSAID use may reduce bladder cancer risk

By Susan Green

Margaret Karagas has found intriguing connections between the use of certain painkillers and the risk of bladder cancer.

As an epidemiologist interested in the causes and prevention of cancer, Margaret Karagas, Ph.D., was intrigued by early reports suggesting that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) might prevent the development of bladder cancer.

Bladder cancer is a very common urologic malignancy. While the prognosis is typically favorable, recurrences are common and progression in disease is possible. In northern New England, both the incidence and mortality rate of bladder cancer are higher than the national average.

Karagas wants to know why that is and to determine whether aspects of diet, lifestyle, or other environmental factors might increase or reduce the occurrence of bladder cancer.

Her interest in cancer began during childhood. An aptitude for math and an early fascination with biology led to an interest in the wonders of the human body. When the beloved priest—a nonsmoker—of her family's Greek Orthodox Church died from lung cancer, she became interested in how someone with healthy habits could develop a cancer that is clearly linked to smoking.

"This tragic event sparked my curiosity about why some people developed cancer and other apparently similar people didn't," Karagas recalls. "Discovering the causes of disease enables us to find ways of preventing it," she says. Additionally, her work can reveal markers of cancer's progression and inform the treatment of patients.

In 2007, she and her colleagues published a population-based study conducted in New Hampshire on the relationship between cancer and analgesic usage. Painkillers containing a now-discontinued drug—phenacetin—are a known carcinogen and suspected of being related to bladder cancer. Participants who had taken phenacetin before its withdrawal from the market appeared to be at greater risk, but Karagas observed a reduced risk of bladder cancer among users of other NSAIDs, such as aspirin.

Based on these early findings, Karagas, a professor of community and family medicine at Geisel and co-director of the Cancer Epidemiology and Chemoprevention program at Norris Cotton Cancer Center, and her colleague, Richard Waddell, D.Sc., a research assistant professor of medicine at Geisel, were approached by the Intramural Program at the National Cancer Institute to collaborate and expand the project regionally to include Maine and Vermont.

She became interested in how someone with healthy habits could develop a cancer that is clearly linked to smoking.

In 2012, they began looking further for connections between analgesics and bladder cancer. Karagas also studied 39 genes related to NSAID metabolism and a newer class of NSAIDs known as selective cyclooxygenase (COX-2) inhibitors.

Findings from this study suggest regular use—and particularly regular use over 10 years or more—of ibuprofen may reduce bladder cancer risk in individuals carrying a gene variant related to NSAID metabolism. Expecting a similar trend for selective COX-2 inhibitors, the researchers instead observed an increased risk of bladder cancer.

Noting that further investigation is needed, Karagas warns against leaping to conclusions or making recommendations.

"A growing body of literature suggests certain NSAIDs may reduce risk of bladder cancer, particularly in individuals with specific genetic traits," she says. "NSAIDs are a worthy area of pursuit—they may also reduce risk for other diseases and cancers."

The results were published in the International Journal of Cancer.

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Geisel School of Medicine at DartmouthDartmouth-Hitchcock Medical CenterWhite River Junction VAMCNorris Cotton Cancer CenterDartmouth College