INFLUENCE OF CIGARETTE-SMOKING AND SCHISTOSOMIASIS ON P53 GENE MUTATION IN UROTHELIAL CANCER

The mutation patterns of the p53 tumor suppressor gene have been shown to reflect the specific carcinogen(s) involved, or the epidemiologica l background in some cancers. To elucidate the impact of cigarette smo king or bilharzial infection on the p53 gene mutation pattern, 61 case s of urothelial cancer from Japan and 7 cases of bladder cancer with s chistosomiasis from Egypt were examined for mutations of the p53 gene. In total, p53 gene mutations were detected in 20 Japanese cases (33%) and 6 Egyptian cases (86%). Although the incidence of p53 gene mutati on was not significantly influenced by habitual smoking, a different m utation pattern was observed as follows: 4 of 10 mutations in smokers in Japan were A:T to G: C transitions, whereas such mutations were not detected in any of 10 mutations in nonsmokers, or in any of 6 mutatio ns associated with schistosomiasis. Although no specific mutation patt ern was detected for the squamous cell carcinomas with schistosomiasis , all 8 base substitutions observed in tumors with squamous cell carci nomas occurred at G:C sites, whereas base substitutions at A:T sites w ere observed in 33% (6 of 18) of mutations in transitional cell carcin omas. Our results suggest that cigarette smoking may have a significan t impact on the mutations of the p53 gene in urothelial cancers. Furth ermore, the distinct spectrum of the p53 gene mutation found in tumors with squamous cell carcinomas may reflect their unique etiological ba ckgrounds.