Analgesic use and the risk of renal cell carcinoma – Findings from the Consortium for the Investigation of Renal Malignancies (CONFIRM) study

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Background

Renal cell carcinoma (RCC) accounts for more than 90% of cancers involving the kidney [1] . The most common subtype is clear cell RCC, followed by papillary and chromophobe types, which are thought to be aetiologically distinct. RCC is the ninth most commonly diagnosed cancer in men living in countries with a high or very high human development index [2] , affecting men approximately twice as often as women [3] . In Australia, as in most developed countries, the incidence of RCC increased by almost 40% in the period 1982–2013 [3] . This has been attributed to the increased use of abdominal imaging, resulting in the incidental detection of small, early-stage, indolent tumours. However the incidence of more advanced cancers has also risen, suggesting that the increase is not driven purely by incidental screen detected diagnoses but also by changes in the prevalence of both known risk factors (such as obesity) and as yet unknown risk factors [4] .

Analgesics such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, are among the most heavily consumed non-prescription pharmaceutical products worldwide and their use has risen over the past 20 years 567 . Laboratory studies have demonstrated that NSAID use can result in acute renal toxicity at therapeutic doses [89] . Clinically, NSAIDs are recognized to have nephrotoxic effects [10] , particularly in combination with other drugs (such as angiotensin-converting enzyme inhibitors) [11] and for particular patient groups such as those with chronic renal failure [12] . Paracetamol, also known as acetaminophen, is a widely used and effective analgesic and antipyretic drug. The analgesic phenacetin, of which acetaminophen is an active metabolite, has been banned in most countries since the late 1970 s [13] when its use was confirmed to increase the risk of renal papillary necrosis [1415] and renal pelvic, ureteric and bladder cancer, by 4–8 fold 161718 .

It has been proposed that the use of NSAIDs and other analgesics such as paracetamol may increase the risk of renal cancer, yet findings from epidemiological studies have been inconsistent. A systematic review conducted in 2000 [19] found no association between the use of aspirin or paracetamol and RCC as did a cohort study [20] published in 2013. Conversely, other case-control studies [2122] and meta-analyses have reported a positive association [2223] .

Our aim was to investigate associations between use of the analgesics aspirin, non-aspirin NSAIDs and paracetamol and risk of RCC using the CONsortium For the Investigation of Renal Malignancies (CONFIRM) Study.