Freedman A N, Michalek A M, Marshall J R, Mettlin C J, Petrelli N J, Black J D, Zhang Z F, Satchidanand S, Asirwatham J E
Department of Educational Affairs, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Cancer Epidemiol Biomarkers Prev. 1996 Apr;5(4):285-91.
Although familial and dietary factors are recognized as important risk determinants for colorectal tumorigenesis, the specific causes of colorectal cancer remain unclear. Studies of p53 genetic alterations have provided clues concerning the etiology of many cancers. This study was designed to determine whether overexpression of the p53 protein is associated with familial and dietary risk factors. Epidemiological data were obtained from 163 colorectal cancer cases and 326 healthy controls. Tumors of all patients were analyzed immunohistochemically for p53 overexpression using an avidin-biotin immunoperoxidase procedure and polyclonal anti-p53 antibody CM1. Of patient tumors, 44.8% showed p53 nuclear reactivity. Colorectal cases versus controls were three times more likely to report a family history of colorectal cancer [odds ratio (OR), 3.12; 95% confidence interval (CI), 1.77-5.52]. Only cruciferous vegetables exhibited a significant inverse association (OR, 0.59; 95% CI, 0.34-1.02; trend test, P = 0.03) for the highest versus lowest quartiles. Both meat and beef displayed an elevated increase in risk. When cases with p53 overexpression (p53 positive) were compared with cases without p53 overexpression (p53 negative), etiological heterogeneity was suggested for family history of colorectal cancer (OR, 0.39; 95% CI, 0.16-0.93), cruciferous vegetables (trend test, P = 0.12), and beef consumption (trend test, P = 0.08). To estimate the individual relative risks for p53-dependent and p53-independent pathways, each p53 subtype was compared with controls. Cruciferous vegetables exhibited a significant association (OR, 0.37; 95% CI, 0.17-0.82; trend test, P = 0.03) when p53 positive cases were compared with controls. When p53 negative cases were compared with controls, a significant increase in risk was observed for family history of cancer (OR, 4.46; 95% CI, 2.36-8.43) and beef (OR, 3.17; 95% CI, 1.83-11.28; trend test, P = 0.006). The p53 (positive) dependent pathway was characterized by an inverse association with cruciferous vegetables, and p53-independent tumors were characterized by family history and beef consumption. These data may indicate the significance of linking epidemiology and molecular biology in assessing specific etiological pathways.
尽管家族因素和饮食因素被认为是结直肠癌发生的重要风险决定因素，但结直肠癌的确切病因仍不清楚。对p53基因改变的研究为许多癌症的病因提供了线索。本研究旨在确定p53蛋白的过表达是否与家族和饮食风险因素相关。从163例结直肠癌病例和326例健康对照中获取流行病学数据。使用抗生物素蛋白-生物素免疫过氧化物酶法和多克隆抗p53抗体CM1，对所有患者的肿瘤进行免疫组织化学分析，以检测p53过表达情况。在患者肿瘤中，44.8%显示p53核反应性。结直肠癌病例与对照相比，报告有结直肠癌家族史的可能性高出三倍[比值比（OR），3.12；95%置信区间（CI），1.77 - 5.52]。仅十字花科蔬菜在最高四分位数与最低四分位数之间呈现出显著的负相关（OR，0.59；95% CI，0.34 - 1.02；趋势检验，P = 0.03）。肉类和牛肉的风险均有升高。当将p53过表达的病例（p53阳性）与无p53过表达的病例（p53阴性）进行比较时，结直肠癌家族史（OR，0.39；95% CI，0.16 - 0.93）、十字花科蔬菜（趋势检验，P = 0.12）和牛肉消费（趋势检验，P = 0.08）提示存在病因异质性。为了估计p53依赖和p53非依赖途径的个体相对风险，将每个p53亚型与对照进行比较。当p53阳性病例与对照比较时，十字花科蔬菜呈现出显著相关性（OR，0.37；95% CI，0.17 - 0.82；趋势检验，P = 0.03）。当p53阴性病例与对照比较时，癌症家族史（OR，4.46；95% CI，2.36 - 8.43）和牛肉（OR，3.17；95% CI，1.83 - 11.28；趋势检验，P = 0.006）的风险显著增加。p53（阳性）依赖途径的特征是与十字花科蔬菜呈负相关，而p53非依赖肿瘤的特征是家族史和牛肉消费。这些数据可能表明在评估特定病因途径时将流行病学与分子生物学联系起来的重要性。
