COX-2 Inhibitors Significantly Reduce Risk of Cancer

"We believe this is the first study to show that selective COX-2 inhibitors have significant chemopreventive effects against breast cancer," says Dr. Randall Harris, professor and director of the Center for Molecular Epidemiology and Environmental Health in The Ohio State University College of Medicine and lead author of the study.

The results come from a larger, case-control study of NSAID use and its impact upon the four leading types of cancer in the United States: breast, lung, prostate and colon cancer. NSAIDs are non-steroidal, anti-inflammatory drugs that block the COX-2 enzyme pathway that is often activated in inflammation, cancer, heart disease and other disorders.

Harris and his colleagues studied the use of celecoxib (Celebrex), rofecoxib (Vioxx), regular aspirin, low-dose aspirin, ibuprofen and acetaminophen among 323 women with breast cancer from 1999-2004.

They compared the results with those from a control group of 649 cancer-free women matched for age, race and county of residence.

They discovered that women who used NSAIDs on a regular basis had less breast cancer. Specifically, they found that those who used celecoxib or rofecoxib for at least two years appeared to benefit the most, experiencing a 71 percent reduction in risk of breast cancer. Ibuprofen use over the same period was associated with a 64 percent reduction, while regular aspirin offered a 51 percent reduction in risk of the disease.

On the other hand, acetaminophen, which has a negligible effect upon COX-2 activity, and low-dose aspirin provided no significant change in the risk of breast cancer.

"The COX-2 signaling pathway is important in cancer because when it's activated, it can stimulate many key steps in cancer development, including cell division, inhibition of cell death, angiogenesis (the creation of new blood vessels to nourish growing tumors) and metastasis," says Harris, who is also a member of the OSU Comprehensive Cancer Center.

Harris says his research group is only midway through analyzing data from the other parts of the study, but adds that early results suggest that regular use of selective COX-2 inhibitors appears to provide about the same magnitude of protection from prostate, lung and colon cancer.

"These results suggest strong potential for regular use of these drugs in cancer prevention. Still, we know these drugs may have side effects, so we are not advising people to go out and start taking them until more studies confirm that they are safe and effective," says Harris.

Celebrex is still widely used for pain relief, but Vioxx was pulled off the market in 2004 following reports of heightened risk of heart attacks.

"It's clear that we need to have multiple retrospective and prospective studies to validate these findings," says Harris, who has been studying the impact of COX-2 inhibitors for many years. "Eventually, we may find that regular intake of a low dose of a COX-2 inhibitor may be enough to reset the COX-2 cascade and safely protect people against cancer."

Grants from Pfizer and the National Cancer Institute supported the study.

Study co-authors include Joanne Beebe-Donk and Galal Alshafie, both colleagues in the Center for Molecular Epidemiology and Environmental Health in the OSU College of Medicine.

The Ohio State University Medical Center

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COX-2 Inhibitors Significantly Reduce Risk of Cancer