Phenacetin‐Containing Analgesics and Cancer of the Bladder or Renal Pelvis in Women

Abstract

In a case-control investigation of 154 women with cancer of the bladder and 440 female population controls spanning the same age range, the relative risk for this cancer was 2.6 in consumers of phenacetin-containing analgesics and 2.7 in tobacco smokers. The relative risks for cancer of the renal pelvis, determined for 31 cases, were 5.4 with phenacetin and 4.7 with tobacco. Increasing consumption of either agent increased the risk for cancer at each of the two sites, while a synergistic rather than purely additive effect was apparent when both phenacetin-containing analgesics and tobacco had been taken. Consumption of analgesic preparations which contained no phenacetin did not increase the risk of developing cancer at either site. The evidence indicates that phenacetin is a clinically important carcinogen for the lower as well as for the upper urinary tract.

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).…”

“…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). Experimental studies have found phenacetin to cause bladder cancer in rats (Johansson, 1981;Murai et al, 1993).…”

“…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).…”

Nonsteroidal antiinflammatory drug use and risk of bladder cancer in the health professionals follow‐up study

“…35 The association between acetaminophen, a major metabolite of phenacetin and bladder cancer risk has also been examined. In previous studies, phenacetin has been shown to be positively associated with risk of bladder cancer [36][37][38][39] and other transitional cell carcinomas in the renal pelvis and ureter. 37,38,[40][41][42][43] Additionally, animal studies have shown that acetaminophen can induce urinary bladder carcinomas in rats 44 and mice.…”

“…In previous studies, phenacetin has been shown to be positively associated with risk of bladder cancer [36][37][38][39] and other transitional cell carcinomas in the renal pelvis and ureter. 37,38,[40][41][42][43] Additionally, animal studies have shown that acetaminophen can induce urinary bladder carcinomas in rats 44 and mice. 45 However, no associations have been reported between acetaminophen and bladder cancer risk in most, 21,39,46,47 but not all, 33 observational studies.…”