Huang Chi-Chou, Cheng Ya-Wen, Chen Meng-Cheng, Lin Yu-Shyang, Chou Ming-Chih, Lee Huei
Colorectal Division, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China.
Environ Mol Mutagen. 2006 Aug;47(7):527-32. doi: 10.1002/em.20222.
Epidemiological studies consistently find associations between colorectal cancer and cigarette smoking; however, there are little molecular data supporting the association. To examine the relationship between cigarette smoking and colorectal cancer, we compared p53 mutation patterns in colorectal tumors from smokers and nonsmokers. In this study, 153 tumor tissues from colorectal cancer patients, including 63 smokers and 90 nonsmokers, were examined for p53 mutation and p53 protein expression by direct sequencing and immunohistochemistry (IHC), respectively. p53 mutations were detected in 77 of 153 (50.3%) colorectal tumors, and no difference was observed in the p53 mutation frequencies in tumors from smokers and nonsmokers (33 of 63, 50.8% for smokers vs. 44 of 90, 48.9% for nonsmokers, P = 0.743). IHC showed that p53-immunoreactive tumors were positively correlated with p53-mutated tumors (P < 0.0001). G:C-->A:T transition and G:C-->T:A transversion were the predominant types of mutations detected in the tumor p53 genes. G:C-->A:T mutation was relatively more common in nonsmokers than in smokers (93.5% for nonsmokers vs. 77.3% for smokers), although this difference was not significant. The frequency of deletion mutation in smoker tumors, however, was significantly higher than that in nonsmoker tumors (7 of 33, 21.2% for smokers vs. 1 of 44, 2.3% for nonsmokers, P = 0.01). Although there were only a few cases of p53 deletion mutation in this study, the observation of a higher frequency of p53 deletion mutation in smoker tumors supports the association between cigarette smoking and the development of colorectal cancer.
流行病学研究一直发现结直肠癌与吸烟之间存在关联；然而，几乎没有分子数据支持这种关联。为了研究吸烟与结直肠癌之间的关系，我们比较了吸烟者和非吸烟者结直肠肿瘤中的p53突变模式。在本研究中，分别通过直接测序和免疫组织化学（IHC）检测了153例结直肠癌患者的肿瘤组织中的p53突变和p53蛋白表达，其中包括63名吸烟者和90名非吸烟者。在153例（50.3%）结直肠肿瘤中检测到p53突变，吸烟者和非吸烟者肿瘤中的p53突变频率没有差异（63例中有33例，吸烟者为50.8%；90例中有44例，非吸烟者为48.9%，P = 0.743）。免疫组织化学显示，p53免疫反应性肿瘤与p53突变肿瘤呈正相关（P < 0.0001）。G:C→A:T转换和G:C→T:A颠换是在肿瘤p53基因中检测到的主要突变类型。G:C→A:T突变在非吸烟者中相对比吸烟者更常见（非吸烟者为93.5%，吸烟者为77.3%），尽管这种差异不显著。然而，吸烟者肿瘤中的缺失突变频率明显高于非吸烟者肿瘤（33例中有7例，吸烟者为21.2%；44例中有1例，非吸烟者为2.3%，P = 0.01）。尽管本研究中只有少数p53缺失突变病例，但吸烟者肿瘤中p53缺失突变频率较高的观察结果支持了吸烟与结直肠癌发生之间的关联。
