NSAIDs and Statins Have No Impact on Renal Cell Carcinoma Risk

Lisly Chéry, MD

Neither nonsteroidal anti-inflammatory drugs (NSAIDs) nor statins influence the development of renal cell carcinoma (RCC), investigators announced at the American Urological Association 2012 Annual Scientific Meeting held May 19-23 in Atlanta, Georgia.

The data, from an ongoing cohort study conducted in western Washington state, appear to undercut prior research suggesting that NSAIDs may increase RCC risk and that statins may reduce RCC risk.

Lisly Chéry, MD, a urology resident at the University of Washington School of Medicine in Seattle, and colleagues determined the effect of NSAIDs and statins on the risk of RCC by prospectively following 77,048 individuals aged 50 to 76 years who were enrolled in the VITamins And Lifestyle (VITAL) Study. The VITAL Study is a cohort study of the associations of supplement use with cancer risk.

Renal cell carcinoma, the most common type of kidney cancer, is the sixth most common cancer in men and the eighth most common cancer in women, Chéry pointed out. Over 64,000 new cases will be diagnosed in 2012, with over 13,000 expected deaths. The incidence of RCC, as with other forms of kidney cancer, is increasing, largely because of an increase in established risk factors such as obesity, hypertension, and smoking.

While numerous risk factors for RCC have been identified, there are limited data on preventive pharmacologic agents, he added. NSAIDs have been shown to protect against colon, breast, and lung cancer, and this protective effect has been largely attributed to their ability to reduce inflammation and cell proliferation. However, data, mostly from retrospective studies, suggest that this class of agents may actually boost the risk of RCC.

The cholesterol-lowering statin drugs have also demonstrated an association with RCC, Chéry noted. However, while statins have been shown to suppress metastasis in animal models of RCC, their effect on RCC in humans is as yet unknown.

At the time of enrollment, participants in the VITAL study completed a gender-specific questionnaire that focused on their dietary habits, medical and family history, and cancer risk factors.

Incident cases of RCC were identified via linkage to the local Surveillance, Epidemiology, and End Results (SEER) Program cancer registry. Overall, 249 cases of RCC were detected.

The investigators found that the observed associations between NSAIDs and statins and RCC risk did not persist after adjusting for known risk factors for RCC, including age, gender, race, lifestyle, and hypertension, diabetes, viral hepatitis, and renal disease.

Compared to nonusers of aspirin and nonaspirin NSAIDs, low (hazard ratio [HR] = 1.2; 95% CI, 0.8-1.6) and high (HR = 1.4; 95% CI, 1.0-2.0) users of NSAIDs had an increased risk of RCC in the base model (P-trend 0.03). Ten-year use of aspirin and other NSAIDs was categorized as none, low use (1-3 days/week or <4 years), or high-use (≥4 days/week and ≥4 years).

However, this relationship was attenuated and nonsignificant (P-trend 0.35) in the multivariate model for both low (HR = 1.01; 95% CI, 0.7-1.4) and high (HR = 1.2; 95% CI, 0.8-1.7) users compared to nonusers.

In the base model, statin use over the prior 2 weeks was associated with an increased risk of RCC (HR = 1.4; 95% CI, 1.0-1.8) but did not maintain significance in the multivariate model (HR = 1.1; 95% CI, 0.8-1.4).

“This will not be the final study on NSAIDs, statins, and kidney cancer,” Chéry said. “The best study would be a randomized controlled study, but those are often difficult to organize.”

Chéry L, Wright J, Hotaling J, et al. NSAID and statin use and risk of renal cell carcinoma. Presented at the American Urological Association Annual Meeting; May 19-23, 2012; Atlanta, GA. Abstract 575.