Does Paracetamol Cause Urothelial Cancer or Renal Papillary Necrosis?

Abstract

The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

“…Johansson and Wahlqvist (1977) reviewed a series of case reports which documented bladder cancer among individuals with a history of phenacetin abuse. These uncontrolled observations were later followed by a few case-control studies (Fokkens, 1979;McCredie et al, 1983;Piper et al, 1985;McCredie and Stewart, 1988). Although fairly strong associations between regular use and increased risk were found in these studies, a dose-response relationship was demonstrated only in the Australian study (McCredie et al, 1983).…”

“…Acetaminophen has been examined as a separate risk factor for bladder cancer in both an Australian and a US study (Piper et al, 1985;McCredie and Stewart, 1988). The results suggested that heavy use of acetaminophen-containing analgesics does not increase bladder cancer risk.…”

“…Phenacetin-based analgesics have been known for a long time to cause cancer of the renal pelvis in humans (Hultengren et al, 1965;Angervall et al, 1969) and experimental data indicates that the compound is carcinogenic to the bladder as well (Johansson, 1981;Murai et al, 1993). Epidemiological data regarding bladder cancer risk are relatively sparse, but generally are in support of phenacetin as a human bladder carcinogen (Fokkens, 1979;McCredie et al, 1983;Piper et al, 1985;McCredie and Stewart, 1988). Acetaminophen use, a phenacetin metabolite, has been examined as a separate risk factor in a few epidemiological (Piper et al, 1985;McCredie et al, 1988;Derby et al, 1996) and experimental studies (Flaks et al, 1985;Hiraga et al, 1985).…”

“…Epidemiological data regarding bladder cancer risk are relatively sparse, but generally are in support of phenacetin as a human bladder carcinogen (Fokkens, 1979;McCredie et al, 1983;Piper et al, 1985;McCredie and Stewart, 1988). Acetaminophen use, a phenacetin metabolite, has been examined as a separate risk factor in a few epidemiological (Piper et al, 1985;McCredie et al, 1988;Derby et al, 1996) and experimental studies (Flaks et al, 1985;Hiraga et al, 1985). On balance, the evidence points towards acetaminophen as being non-carcinogenic to the bladder.…”

Cancer risk in persons receiving prescriptions for paracetamol: A Danish cohort study

“…The epidemiologic results for transitional cell cancers of the urinary bladder, ureter and renal pelvis, all derived from case-control studies, are also inconsistent. 2,5,7-14 Most studies of cancer of the renal pelvis and ureter have been small, 2,7,10 because of the rarity of these tumors, and the early studies reporting positive associations [7][8][9][10] may not have been able to discriminate between risks associated with earlier phenacetin use and more recent use of paracetamol. In the largest study of renal pelvis and ureter cancer to date, 12 no association with paracetamol use was seen.…”