Certain analgesics have been associated with an increased risk for renal cell carcinoma (RCC), particularly among patients who use the medications for longer durations.

Excluding aspirin, the relative risk for RCC was 1.51 (95% CI: 1.12-2.04) among nonsteroidal anti-inflammatory users, prospective data published in the Journal of the American Medical Association’s Archives of Internal Medicine indicate.

Furthermore, the relative risk was higher with each increase in duration of use:

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  • Four years or less — RR=0.81 (95% CI: 0.59 to 1.11)
  • Four to 10 year —  RR=1.36 (95% CI: 0.98 to 1.89)
  • 10 or more years — RR=2.29 (95% CI: 1.71 to 5.01; P<0.001 for trend)

An estimated 60 million Americans use NSAIDs on a regular basis, according to background information published in an accompanying editor’s note.

“Risks and benefits should be considered in deciding whether to use analgesics; if our findings are confirmed, an increased risk of RCC should also be considered,” study researcher Eunyoung Cho, ScD, and colleagues from Harvard Medical School wrote.

Although aspirin and other NSAIDs are thought to protect against some types of cancer, epidemiologic data from small case-control studies have suggested a possible link between analgesics and renal cell carcinoma.

To further investigate this association, Cho and colleagues analyzed data from 77,525 women who participated in the Nurses’ Health Study and 49,403 men from the Health Professionals Follow-Up Study.

Analgesic-use data were collected in questionnaires administered to participants at baseline and every two years for a follow-up duration of 16 years for the women and 20 years for the men. Participants were considered regular users if they took a single type of analgesic twice a week or more.

The researchers determined that 24% of the women were regular aspirin users, 18% took non-aspirin NSAIDs and 15.5% used acetaminophen.

Among the men, 29.4% regularly used aspirin, whereas 18.8% regularly took non-aspirin NSAIDs and 5.7%, acetaminophen.

A total of 333 renal cell carcinoma cases were identified among women and 150 cases in men during the follow-up periods.

In multivariate analyses, aspirin use was not associated with increased renal cell carcinoma risk for women (RR=0.93; 95% CI: 0.64-1.35), men (RR=0.99; 95% CI: 0.71-1.37) or both groups pooled  (RR= 0.96; 95% CI: 0.75-1.23).

However, the researchers observed a slight increased risk with acetaminophen use. Among women, the RR was 0.93 (95% CI: 95% CI 0.84 -1.88); for men the RR was 1.47 (95% CI: 0.84-2.56); in pooled analysis the RR was 1.32 (95% CI: 0.96-1.84).

“Acetaminophen is a metabolite of phenacetin, which was banned in the 1970s to 1980s worldwide because of its carcinogenic effect, especially in renal pelvis tumors,” the researchers pointed out.

Because more detailed information was available for women, the researchers were able to get a better idea of the risk for RCC with non-aspirin NSAIDs used at different frequencies. Women who took the medications for four days or fewer per month had a RR of 1.08 (95% CI: 0.67 to 1.74) vs. a RR of 1.86 (95% CI: 1.19 to 2.90) among women who took NSAIDs for 15 days or more.

Absolute risk differences for female and male users of non-aspirin NSAIDs compared with nonusers were 9.15 and 10.92 per 100,000 person-years, respectively.

Cho E et al. Arch Intern Med. 2011;171: 1487-1493.