TOBACCO SMOKING, OCCUPATION, AND P53 NUCLEAR OVEREXPRESSION IN EARLY-STAGE BLADDER-CANCER

Epidemiological studies show an increased risk of bladder cancer assoc iated with tobacco smoking and occupational exposures. Certain carcino gens in tobacco and occupational exposures cause DNA damage and may pr oduce specific mutations. TP53 is considered a common target for carci nogenic agents, and mutations of this gene are reported to be the most frequent nuclear abnormalities in human cancer. In order to investiga te the relationship between tobacco smoking, occupations, and altered patterns of p53 expression, we have analyzed a group of 109 incident p atients with superficial transitional cell carcinoma of the bladder. W e assessed p53 nuclear overexpression by the use of anti-p53 antibody PAb1801 and immunohistochemistry, and identified 45 of 109 patients (4 1%) displaying p53-positive phenotype. We observed a significant assoc iation between the number of cigarettes smoked per day and p53 nuclear overexpression (p = 0.02). The odds ratios were 2.3 for those smoking 1-2 packs per day and 8.4 for smoking more than 2 packs per day. Simi lar estimates were obtained after controlling for age, sex, and race. Elevated odds ratios were also observed for dye-/ink-related (odds rat io = 2.0; 95% Cl, 0.4-9.4) and cooking-related occupations (1.8, 0.6-5 .0), although those were not statistically significant. These data sup port the hypothesis that certain carcinogens derived from cigarette sm oking and occupations may induce TP53 mutations, which in turn are inv olved in early steps of bladder carcinogenesis.