Link Found Between Long-Term Nonaspirin NSAIDs and Renal Cell Carcinoma

Eunyoung Cho, ScD

According to an analysis of 2 large prospective studies of men and women, the use of nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs) is associated with an increased risk of renal cell carcinoma (RCC). The risk is especially pronounced in long-term NSAID users.

Eunyoung Cho, ScD, with Harvard Medical School and Brigham and Women’s Hospital in Boston, Massachusetts, and associates assessed the use of aspirin, NSAIDs, and acetaminophen in relation to RCC risk in the all-male Health Professionals Follow-Up Study starting in 1986 and the all-female Nurses’ Health Study starting in 1990, with follow-up every 2 years thereafter.

The analysis relied on responses to questionnaires that sought updated information on lifestyle factors and analgesic use; it also identified new diagnoses of major illnesses, including RCC.

The investigators believe that theirs is the first prospective study of nonaspirin NSAIDs and the largest prospective study of analgesics in relation to RCC risk. Kidney cancer is the seventh most common form of cancer among men and the ninth among women in the United States. RCC is responsible for 85% of all cases of kidney cancer.

Analgesics are among the most widely used prescription and over-the-counter drugs in the United States, and some of them are known to exert a protective effect against cancer. While epidemiologic data that are largely drawn from case-control studies have reported a possible association between analgesic use and RCC risk, most prospective studies of analgesics and kidney cancer have been limited by a small sample size and a short duration of follow-up.

Overall, 153 cases of RCC were documented in the 77,525 women who were followed for 16 years, and 180 cases of RCC were documented in the 49,403 men who were followed for 20 years.

Regular use of nonaspirin NSAIDs at baseline was associated with an increased RCC risk, with a pooled multivariate relative risk of 1.51 (95% confidence interval [CI], 1.12- 2.04) compared with nonregular use. There was no association between aspirin and acetaminophen and RCC risk.

The analysis revealed a dose-response relationship between regular use of nonaspirin NSAIDs and RCC risk. The pooled multivariate relative risks were 0.81 (95% CI, 0.59-1.11) for <4 years, 1.36 (0.98-1.89) for 4 to 10 years, and 2.92 (1.71-5.01) for 10 or more years (P <.001 for trend).

Cho and associates stressed that the prospective design minimizes potential biases that may limit case-control studies. Also, unlike earlier investigations, their study gathered information on analgesic use several times during follow-up, which allowed them to quantify duration of use. Duration of use is a better predictor of RCC risk for nonaspirin NSAIDs than is baseline use.

“Risks and benefits should be considered in deciding whether to use analgesics,” they wrote. “If our findings are confirmed, an increased risk of RCC should also be considered.”

Cho E, Curhan C, Hankinson SE, et al. Prospective evaluation of analgesic use and risk of renal cell cancer. Arch Intern Med. 2011;171(16):1487-1493. doi:10.1001/ archinternmed.2011.356.