CARCINOMAS OF THE RENAL PELVIS ASSOCIATED WITH SMOKING AND PHENACETIN-ABUSE - P53 MUTATIONS AND POLYMORPHISM OF CARCINOGEN-METABOLIZING ENZYMES

Phenacetin abuse and smoking are established risk factors for transiti onal cell carcinomas of the urinary tract. In the present study, we an alysed exposure and the clinical course of patients who underwent neph rectomy for transitional cell carcinoma of the renal pelvis. PCR-SSCP of archival, paraffin-embedded histological sections followed by direc t DNA sequencing revealed that 29 of 89 (33%) renal pelvic carcinomas contained a p53 mutation. Double mutations were found in 4 tumours and triple mutations in 1 tumour. The incidence of P53 mutations was sign ificantly higher in tumours with grades 3 and 4 than in those with gra des 1 and 2 and higher in invasive than in non-invasive tumours. Furth ermore, patients with carcinomas carrying a p53 mutation showed poorer survival than those without mutation. The type of p53 mutation in ren al pelvic carcinomas was similar to that reported for bladder cancer, G:C-->A:T transition mutations being most frequent (45%, 33% of these at CpG sites), followed by G:C-->T:A and G:C-->C:G transversions. The incidence and type of p53 mutation did not differ significantly in pat ients with a history of phenacetin abuse, smoking or neither of these habits. This was also true for G:C-T:A transversions (17.5% of mutatio ns), wh ich are considered typical of smoking-induced carcinomas at ot her sites, e.g., lung, oral cavity and oesophagus. Our results indicat e that the frequency and pattern of p53 mutations are similar in trans itional cell carcinomas of the bladder and the renal pelvis and do not reflect exposure to phenacetin and/or smoking. The frequency of genet ic polymorphism in genes coding for carcinogen-metabolising enzymes (C YP1A1, NAT1, GSTT1 and GSTM1) was also independent of exposure. Althou gh the sample size of our study does not allow definite conclusions, t hese data are compatible with chronic tissue damage as a causative fac tor in the evolution of urothelial carcinomas rather than pointing to a direct mutagenic effect of phenacetin and tobacco-specific carcinoge ns. Int, J. Cancer (Pred. Oncol.) 79:531-536, 1998, (C) 1998 Wiley-Lis s, Inc.