Zhang Z F, Sarkis A S, Cordon-Cardo C, Dalbagni G, Melamed J, Aprikian A, Pollack D, Sheinfeld J, Herr H W, Fair W R
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):19-24.
Epidemiological studies show an increased risk of bladder cancer associated with tobacco smoking and occupational exposures. Certain carcinogens in tobacco and occupational exposures cause DNA damage and may produce specific mutations. TP53 is considered a common target for carcinogenic agents, and mutations of this gene are reported to be the most frequent nuclear abnormalities in human cancer. In order to investigate the relationship between tobacco smoking, occupations, and altered patterns of p53 expression, we have analyzed a group of 109 incident patients with superficial transitional cell carcinoma of the bladder. We assessed p53 nuclear overexpression by the use of anti-p53 antibody PAb1801 and immunohistochemistry, and identified 45 of 109 patients (41%) displaying p53-positive phenotype. We observed a significant association 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. Similar estimates were obtained after controlling for age, sex, and race. Elevated odds ratios were also observed for dye-/ink-related (odds ratio = 2.0; 95% CI, 0.4-9.4) and cooking-related occupations (1.8, 0.6-5.0), although those were not statistically significant. These data support the hypothesis that certain carcinogens derived from cigarette smoking and occupations may induce TP53 mutations, which in turn are involved in early steps of bladder carcinogenesis.
流行病学研究表明，吸烟和职业暴露会增加患膀胱癌的风险。烟草和职业暴露中的某些致癌物会导致DNA损伤，并可能产生特定的突变。TP53被认为是致癌物的常见靶点，据报道该基因的突变是人类癌症中最常见的核异常。为了研究吸烟、职业与p53表达改变模式之间的关系，我们分析了一组109例新发浅表性膀胱移行细胞癌患者。我们使用抗p53抗体PAb1801和免疫组织化学评估p53核过表达，在109例患者中鉴定出45例（41%）表现出p53阳性表型。我们观察到每天吸烟数量与p53核过表达之间存在显著关联（p = 0.02）。每天吸1 - 2包烟者的优势比为2.3，每天吸超过2包烟者的优势比为8.4。在控制年龄、性别和种族后获得了类似的估计值。在与染料/油墨相关职业（优势比 = 2.0；95%可信区间，0.4 - 9.4）和烹饪相关职业（1.8，0.6 - 5.0）中也观察到优势比升高，尽管这些没有统计学意义。这些数据支持这样的假设，即来自吸烟和职业的某些致癌物可能诱导TP53突变，进而参与膀胱癌发生的早期阶段。
