According to research published in the Archives of Internal Medicine, the long-term use of non-aspirin NSAIDs may increase the risk of renal cell cancer (RCC).

The authors note that some epidemiological data (mainly case-control studies) suggest an association between analgesic use and an increased risk of RCC; most prospective studies in this area have been small and involved a short follow-up period.  In their study, they examined the use of analgesia and its association with RCC in two prospective studies – the Nurses' Health Study (NHS; included 121,700 female nurses aged 30-55 years in 1976) and the Health Professionals Follow-up Study (HPFS; 51,529 male health professionals aged 40-75 years in 1986).

Follow-up for the current analysis was started in 1990 for the NHS (when use of non-aspirin analgesia was first documented) and at the start of the HPFS; those lacking baseline data on analgesic use and those with a history of cancer were excluded. Both cohorts were sent questionnaires twice a year, to update information on a number of lifestyle factors, including use of analgesia; new diagnoses were also recorded.  Regular users were defined as those who took one type of analgesic medication ≥2 times per week (when information on frequency of use was available) and/or ≥2 tablets per week (when dose information was available).  Follow-up rates among those included were 97.0% in the NHS and 91.0% in the HPFS.  Data on other risk factors for RCC (e.g. smoking, body weight, physical activity, history of hypertension) was collected and considered. RCC (clear cell, papillary, chromophobe, collecting duct RCC, and RCC not otherwise classified) was evaluated as the primary disease endpoint; secondary analyses evaluated clear cell RCC, the major histological subtype.

The main findings reported are as follows:

• During follow-up of 16 years among 77,525 women and 20 years among 49,403 men, there were 333 RCC cases documented.  

• Regular use of non-aspirin NSAIDs was associated with an increased RCC risk; the pooled multivariate relative risk (RR) was 1.51 (95% CI 1.12-2.04) at baseline. The absolute risk differences for users vs. nonusers of non-aspirin NSAIDs were 9.15 per 100 000 person-years in women and 10.92 per 100 000 person-years in men.

• Assuming a causal relation, use of non-aspirin NSAIDs by each of 10,929 women or 9,158 men would lead to one case of RCC (the numbers needed to harm).

• There was a dose-response relationship between duration of non-aspirin NSAID use and RCC risk; and only use for more than ten years had a 95% CI that did not cross 1 (RR 2.92; 95% CI 1.71-5.01 compared with non-regular use).  The overall trend was statistically significant (p<0.001).

• Aspirin and paracetamol use were not associated with RCC risk.

The authors acknowledge a number of limitations to their study, including the possibility of residual confounding and/or confounding by indication (e.g. patients with RCC starting to take analgesics prior to diagnosis to treat symptoms), and the fact that more detailed information on dose of NSAIDs has only recently been collected, with inadequate follow-up to address this issue.  They note that longer follow-up will allow them to carry out a more detailed evaluation of the dose-response relationship between non-aspirin NSAIDs and RCC risk.

They conclude that their data suggest an association between non-aspirin NSAID use and elevated risk of RCC, especially among those taking them for a long duration.  They suggest that the risks and benefits should be carefully considered when deciding whether to use analgesics; an increased risk of RCC should also be considered if these findings are confirmed.  

An accompanying Comment discusses the study.

[Editor’s note: The ‘Behind the Headlines’ service from NHS Choices will be producing a quality assessment of press reports based on this research, to be available via the link below over the next couple of days.]