Different roles for phenacetin and paracetamol in cancer of the kidney and renal pelvis.

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.