Drugs and renal cell cancer

Gago-Dominguez M, Yuan JM, Castelao JE, Ross RK, Yu MC. Regular use of analgesics is a risk factor for renal cell carcinoma.Br J Cancer. 1999 Oct;81(3):542-8.PMID: 10507783 [PubMed - indexed for MEDLINE]

Phenacetin-based analgesics have been linked to the development of renal pelvis cancer and renal cell carcinoma (RCC). The relationship between non-phenacetin types of analgesics and kidney cancer is less clear, although laboratory evidence suggests that these drugs possess carcinogenic potential. A population-based case-control study involving 1204 non-Asian RCC patients aged 25-74 and an equal number of sex-, age- and race-matched neighbourhood controls was conducted in Los Angeles, California, to investigate the relationship between sustained use of analgesics and risk of RCC according to major formulation categories. Detailed information on medical and medication histories, and other lifestyle factors was collected through in-person interviews. Regular use of analgesics was a significant risk factor for RCC in both men and women (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.4-1.9 for both sexes combined). Risks were elevated across all four major classes of analgesics (aspirin, non-steroidal anti-inflammatory agents other than aspirin, acetaminophen and phenacetin). Within each class of analgesics, there was statistically significant increasing risk with increasing level of exposure. Although there was some minor variability by major class of formulation, in general individuals in the highest exposure categories exhibited approximately 2.5-fold increase in risk relative to non- or irregular users of analgesics. Subjects who took one regular-strength (i.e. 325 mg) aspirin a day or less for cardiovascular disease prevention were not at an increased risk of RCC (OR = 0.9, 95% CI = 0.6-1.4).

Chow WH, McLaughlin JK, Linet MS, Niwa S, Mandel JS. Use of analgesics and risk of renal cell cancer.Int J Cancer. 1994 Nov 15;59(4):467-70.PMID: 7960214 [PubMed - indexed for MEDLINE]

Although heavy or long-term use of analgesics has been related to risk of renal cell cancer in several studies, evidence for such an association remains inconclusive. In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with lifetime consumption among those who reported during in-person interviews regular (at least 2 or more times per week for 1 month or longer) use of analgesics. Odds ratios (OR) were computed using logistic regression analyses. No excess risk was associated with regular use of aspirin, acetaminophen, phenacetin or combinations of these agents, nor did risks rise with increasing cumulative intake of these analgesics. A non-significant increased risk (OR = 2.1, 95% CI = 0.6-6.9) was observed among women who used only acetaminophen-containing analgesics, but little excess was seen in men. Earlier studies reported a link to phenacetin-containing analgesics, but no one reported exclusive use of phenacetin-containing drugs in our study. The findings suggest that use of analgesics is not likely to play a major role in renal cell cancer development and that for cases diagnosed in the late 1980s or later, after the earlier withdrawal of phenacetin-containing drugs from the market, a hazard from this analgesic no longer exists.

McCredie M, Stewart JH, Day NE.Different roles for phenacetin and paracetamol in cancer of the kidney and renal pelvis.Int J Cancer. 1993 Jan 21;53(2):245-9.PMID: 8425761 [PubMed - indexed for MEDLINE]
A population-based case-control study of kidney cancer was carried out in New South Wales using data from structured interviews with 489 cases of renal-cell cancer and 147 cases of renal pelvic cancer diagnosed in 1989 and 1990, together with 523 controls from the electoral rolls. This study showed that the risk of renal pelvic cancer was increased by phenacetin/aspirin compound analgesics (RR = 12.2; 95% CI 6.8-22.2) to a far greater extent than by paracetamol (RR = 1.3; 95% CI 0.7-2.4; not significant). There was a doubling of risk (RR = 2.0; 95% CI 0.9-4.4) in the highest tertile of paracetamol taken in any form compared with values for non-users of any type of analgesic. By contrast, the risk of renal-cell cancer appeared to be increased to a similar degree by phenacetin/aspirin compound analgesics (RR = 1.4; 95% CI 0.9-2.3) and paracetamol taken in any form (RR = 1.5; 95% CI 1.0-2.3). When both drugs were treated as alternative forms of the same risk factor, the risk was increased by 1.7 (95% CI 1.2-2.4). On this evidence, we postulate that phenacetin/aspirin compounds are weakly carcinogenic in the renal parenchyma through the metabolic conversion of phenacetin to paracetamol, and potently carcinogenic in the renal pelvis by different or additional pathways involving renal papillary necrosis. In addition, there is an indication of a weak link between paracetamol and renal pelvic cancer.

Finkle WD, McLaughlin JK, Rasgon SA, Yeoh HH, Low JE. Increased risk of renal cell cancer among women using diuretics in the United States.Cancer Causes Control. 1993 Nov;4(6):555-8.PMID: 8280833 [PubMed - indexed for MEDLINE]
Use of prescription diuretics and incidence of renal cell cancer have increased in the United States in the past 25 years. Recent interview-based epidemiologic studies have reported an association between diuretic use and renal cell cancer risk. Our study evaluated this hypothesis using, for the first time, medical records as the source of the information on prescription diuretic use. Using medical records of women from a prepaid health plan, we identified 191 cases and 191 controls matched on age, membership duration, and membership at diagnosis. Diuretics use and history of potential confounding factors were ascertained by a standardized review of the medical records of each subject, without reference to case or control status. There was a strong and statistically significant association between renal cell cancer and prescription diuretics (odds ratio [OR] adjusted for hypertension, smoking, and obesity = 2.9, 95 percent confidence interval [CI] = 1.7-4.7). Risk tended to increase with dose, measured by number of prescriptions. Since renal cancer can induce hypertension, which is treated by diuretics, and thereby confound the association with diuretics, we examined diuretic use 10 or more years prior to diagnosis when secondary hypertension would be unlikely. The OR for prescriptions 10 or more years before diagnosis was 3.5 (CI = 1.7-7.4). Our results support earlier reports of an excess risk of renal cell cancer among users of prescription diuretics and indicate need for further study to evaluate this relationship, especially due to the extensive use of diuretics and the increasing incidence of this cancer.

McCredie M, Pommer W, McLaughlin JK, Stewart JH, Lindblad P, Mandel JS, Mellemgaard A, Schlehofer B, Niwa S. International renal-cell cancer study. II. Analgesics.Int J Cancer. 1995 Jan 27;60(3):345-9.PMID: 7829242 [PubMed - indexed for MEDLINE]
There has been concern about the role of analgesics in the development of renal-cell cancer, although a few studies have reported moderately elevated risks with regular or long-term use. In a large international case-control study of renal-cell cancer we examined, among other hypotheses, the effect of phenacetin-containing and of other types of analgesics: paracetamol (acetaminophen), salicylates (mainly aspirin) and pyrazolones (e.g., antipyrine or phenazone). Relative risks, adjusted for the effects of age, sex, body-mass index, tobacco smoking and study centre, were not significantly increased with intake of phenacetin, either when lifetime consumption was categorized at the level of > or = 0.1 kg or when subjects were subdivided further by amount. Nor were paracetamol, salicylates or pyrazolones linked with renal-cell cancer. No consistently increasing risks with consumption level was found. The lack of association was not altered by restricting analgesic use to that which occurred 5 or 10 years before the defined "cut-off" date or when analysis was restricted to exclusive users of a particular type of analgesic. Neither was the risk influenced by the rate of consumption or whether the consumption had occurred at a young age. Our study provides clear evidence that aspirin is unrelated to renal-cell cancer risk, and our findings do not support the hypothesis that analgesics containing phenacetin or paracetamol increase the risk, although the number of "regular" users and the amount of these types of analgesic consumed were too small to confidently rule out a minor carcinogenic effect of phenacetin and paracetamol.

Vanchieri C. Australian study links certain analgesics to renal cancers.J Natl Cancer Inst. 1993 Feb 17;85(4):262-3. No abstract available.PMID: 8426370 [PubMed - indexed for MEDLINE]