COLUMBUS, Ohio - Regular use of over-the-counter non-steroidal inflammatory drugs (NSAIDs) such as aspirin and ibuprofen is associated with an increased risk of dying in patients diagnosed with Type 1 endometrial cancers, according to a new population-based study led by The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James).
In this observational study, a multi-institutional team of cancer researchers sought to understand the association of regular NSAID use and the risk of dying from endometrial cancer among a cohort of more than 4,000 patients.
They found that regular NSAID use was associated with a 66 percent increased risk of dying from endometrial cancer among women with Type 1 endometrial cancers, a typically less-aggressive form of the disease. The association was statistically significant among patients who reported past or current NSAID use at the time of diagnosis, but it was strongest among patients who had used NSAIDs for more than 10 years in the past but had ceased use prior to diagnosis. Use of NSAIDs was not associated with mortality from typically more aggressive, Type 2 cancers.
"There is a increasing evidence that chronic inflammation is involved in endometrial cancer and progression and recent data suggests that inhibition of inflammation through NSAID use plays a role," says Theodore Brasky, PhD, co-lead author of the study and a cancer epidemiologist with the OSUCCC - James. "This study identifies a clear association that merits additional research to help us fully understand the biologic mechanisms behind this phenomenon. Our finding was surprising because it goes against previous studies that suggest NSAIDs can be used to reduce inflammation and reduce the risk of developing or dying from certain cancers, like colorectal cancer."
Researchers point out that information about specific dosages and NSAID use after surgery was not available in the current study, which represents a significant limitation.
"We are continuing to analyze the biologic mechanisms by which inflammation is related to cancer progression in this specific cohort of patients," adds Ashley Felix, PhD, co-lead author of the study and cancer epidemiologist with the OSUCCC - James and College of Public Health.
They report their findings in the Dec. 16, 2016, issue of the Journal of the National Cancer Institute.
"These results are intriguing and worthy of further investigation," says David Cohn, MD, gynecologic oncology division director at the OSUCCC - James and co-author of the study. "It is important to remember that endometrial cancer patients are far more likely to die of cardiovascular disease than their cancer so women who take NSAIDs to reduce their risk of heart attack -- under the guidance of their physicians -- should continue doing so. While these data are interesting, there is not yet enough data to make a public recommendation for or against taking NSAIDS to reduce the risk of cancer-related death."
Cohn says any woman concerned about the risks of long-term NSAID use should consult with her physician.
Study Design and Results
For this study, researchers analyzed information from 4,374 endometrial cancer patients who previously participated in a national clinical trial (NRG Oncology/GOG 210). All of the women were eligible for surgery and had not undergone prior surgery or radiation at the time of enrollment. Participants were followed for an average of five years after enrollment.
Study participants were asked at the beginning of the study to complete a questionnaire prior to surgery to capture information about previous and current NSAID use including aspirin, non-aspirin NSAIDs (ibuprofren, naproxen, indomethacin, piroxicam, sulinadac) and COX-2 inhibitors. Researchers collected information about duration of use -- ranging from less than one year to more than 10 years -- and whether that use was previous or current. Daily frequency of NSAID use, NSAID dosage, and use after surgery were not available.
Researchers also collected clinical data (cancer stage, pathology, and treatment), demographic data (age, race, annual income, education) and information about established endometrial cancer risk factors, including body weight/height, reproductive and menstrual characteristics, history of hormone therapy, smoking status and other medical conditions.
Researchers used regression models to statistically account for the influence of these additional factors on the association between NSAID use and endometrial cancer mortality.
Funding for this research comes from grants to the NRG/Gynecologic Oncology Group (CA 27469, CA 37517, 1 U10 CA180822 and U10 CA180868); National Cancer Institute and National Institutes of Health.
Additional collaborators in this study include Louise A. Brinton, PhD, of the National Cancer Institute; D. Scott McMeekin, MD, and Joan Walker, MD, of the University of Oklahoma; David Mutch, MD, and Premal Thaker, MD, Washington University School of Medicine; William Creasman, MD, Medical University of South Carolina; Richard Moore, MD, Women and Infants Hospital/Brown University; Shashikant Lele, MD, and John Boggess, MD, University of North Carolina; Saketh Guntupalli, MD, University of Colorado Cancer Center; Levi Downs, MD, University of Minnesota; Christa Nagel, MD, Case Western Reserve University; Michael Pearl, MD, State University of New York; Olga Ioffe, MD; University of Maryland; and Shamshad Ali, Roswell Park Cancer Institute.
Scope of Endometrial Cancer in the United States
More than 60,000 women are diagnosed with endometrial cancer in the United States annually, making it the fourth most common cancer in women and sixth leading cause of cancer death. The cancer begins in the lining of the uterus and grows outward to surrounding organs. Type 1 tumors are less aggressive and are typically confined to the uterus at the time of diagnosis, whereas Type 2 tumors tend to be aggressive and are at greater risk of spreading. The disease is most common in women over age 60. Aside from aging, excess body weight, diabetes, certain hormone therapies, a family history of endometrial cancer or personal history of endometrial hyperplasia, breast cancer or ovarian cancer are associated with increased risk of the disease.
About The OSUCCC - James
The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs. As the cancer program's 306-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. For more information, please visit cancer.osu.edu.
JNCI Journal of the National Cancer Institute