Phenacetin abuse related to bladder cancer

Fokkens, Wytske

doi:10.1016/0013-9351(79)90097-5

Cited by 26 publications

(9 citation statements)

References 6 publications

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

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confidence: 99%

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Non-steroidal anti-inflammatory drugs and bladder cancer prevention

et al. 2000

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Summary Inclusion of phenacetin among 'proven' human carcinogens by the IARC in 1987, raised concerns about the carcinogenic potential of acetaminophen, its major metabolite. Acetaminophen has been implicated as a possible causal agent in the development of cancer of the renal pelvis. The bladder and renal pelvis, which derive from the same embryological structure, share the same transitional type of epithelium. Past studies have been inconclusive on the possible relationship among these analgesics and bladder cancer but no large, highly detailed study of this association has been conducted. A population-based case-control study conducted in Los Angeles, California, involved 1514 incident bladder cancer cases and an equal number of controls who were matched to the index cases by sex, date of birth (within 5 years) and race. Detailed information on medication use and prior medical conditions was collected through in-person interviews. Regular use of analgesics was not associated with an increased risk of bladder cancer in either men or women. In fact, compared with non-or irregular users, regular analgesic users were at a decreased risk of bladder cancer overall (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68-0.96). However, there were clear differences in both the direction and strength of the associations between the different formulation classes of analgesics and bladder cancer risk. Intake of phenacetin was positively related to bladder cancer risk in a dose-dependent manner while intake of its major metabolite in humans, acetaminophen, was unrelated to risk. Intake of all classes of NSAIDs, except pyrazolon derivatives, were negatively associated with bladder cancer risk, with suggestive evidence that the protective effect varies in strength by subcategories of formulation. Acetic acids seemed to exhibit the strongest protective effect, whereas aspirin/other salicylic acids and oxicam showed the weakest protection.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

et al. 2000

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“…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.…”

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confidence: 90%

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

Genkinger

DeVivo

Stampfer

et al. 2007

Intl Journal of Cancer

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Nonsteroidal antiinflammatory drugs (NSAIDs) use, particularly aspirin, may lower the risk of several cancers, including bladder. NSAIDs may reduce development of bladder tumors by decreasing inflammation, inhibiting cycloxygenase-2, inhibiting proliferation and inducing apoptosis of cancer cells. However, acetaminophen, a major metabolite of phenacetin, may be positively associated with bladder cancer risk. Results from case-control studies on NSAIDs and acetaminophen use and bladder cancer risk are inconsistent. We investigated the association between NSAID and acetaminophen use and bladder cancer risk in a large cohort of US males. Among 49,448 men in the Health Professionals FollowUp Study, 607 bladder cancer cases were confirmed during 18 years of follow-up. Relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models. Multivariate RR were adjusted for age, current smoking status, pack years, geographic region and fluid intake. No significant associations were observed for regular aspirin ( 2 tablets per week), (RR 5 0.99, 95% CI 0.83-1.18), ibuprofen (RR 5 1.11, 95% CI 0.81-1.54), acetaminophen (RR 5 0.96, 95% CI 0.67-1.39) or total NSAID use (not including acetaminophen; RR 5 1.01, 95% CI 0.85-1.20) and bladder cancer risk compared with nonuse. Consistent use (over 6 years) of aspirin, ibuprofen, acetaminophen and total NSAIDs, compared to nonuse, was not associated with bladder cancer risk. No association was observed between aspirin frequency and dose and bladder cancer risk. We observed no effect-modification by smoking, age or fluid intake. Our results suggest that regular NSAID or acetaminophen use has no substantial impact on bladder cancer risk among men. ' 2007 Wiley-Liss, Inc.Key words: bladder cancer; NSAID use; epidemiology; cohort In the US, bladder cancer is the fourth most common cause of cancer among men and the ninth most common cause of cancer death among men. 1 Bladder cancer is approximately 2-4 times more common in males compared to females 2,3 and there is an approximately twofold higher risk among Caucasian compared to African American men. 2 Cigarette smoking, 4,5 occupational exposures to aromatic amines 6-8 and schistosomal infections 9,10 have been associated with risk of bladder cancer. Other environmental factors, including selenium intake, 8 chlorination by-products 11,12 and low dose arsenic levels in water sources, 13,14 have also been associated with bladder cancer, but are less well-established.Epidemiologic evidence suggests that use of nonsteroidal antiinflammatory drugs (NSAIDs), particularly aspirin, may lower the risk of several cancers, 15-20 including bladder cancer. 21 Several epidemiologic studies on urinary tract infections, 22,23 indwelling catheters, 24 bladder stones 25 and schistosomiasis 26 all support a role for inflammation in bladder carcinogenesis. In addition, recent animal and cell line studies show that risk of bladder cancer may be associated with inflammation and upregulation of cycloxygenase-2 (COX-2). 27...

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“…Cyclophosphamide treatment increases the risk of bladder cancer nine-fold [ 9 ]. Chronic abusers of the analgesic phenacetin are at increased risk, estimated at four-fold [ 10 ]. Use of Aristolochia fangchi (a Chinese herb found in some diet pills) is also associated with an increased risk [ 11 ], as is arsenic ingestion [ 12 ].…”

Section: Risk Factorsmentioning

confidence: 99%

Superficial Bladder Cancer

Jackson

Griffiths

Mellon

2014

Urological Oncology

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Defi nitionSuperfi cial bladder cancer refers to a carcinoma of the bladder that is confi ned to the urothelium and/or sub-urothelial connective tissue, without invasion of the muscularis propria. The term "non-muscle invasive bladder cancer" (NMIBC)may be used synonymously. In practice, these terms are principally used to refer to transitional cell carcinoma (TCC), and around 75-85 % of TCCs are superfi cial at presentation. EpidemiologyWorld-wide, there were around 382,000 new bladder tumours diagnosed in 2008, making bladder cancer the 9th commonest cancer [ 1 ]. The incidence is around three-fold higher in men than women. Women, however, tend to present with more advanced disease and have poorer outcomes [ 2 ]. Incidence increases in both sexes from age 50, and the median age at presentation is 70 years.Trends in incidence of bladder cancer are diffi cult to quantify accurately due to variations in the reporting of low-grade lesions. However, there is clear evidence that bladder cancer mortality is falling in the United States [ 3 ], Europe [ 4 ], and world-wide [ 5 ]. This is likely to refl ect reduced exposure to tobacco and occupational carcinogens.

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Phenacetin abuse related to bladder cancer

Cited by 26 publications

References 6 publications

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

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

Superficial Bladder Cancer

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