Cigarette smoking and p53 mutations in lung cancer and bladder cancer
Cigarette smoking and p53 mutations in lung cancer and bladder cancer
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DOI：
10.2307/3432822
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发表时间：
1996-05-01
影响因子：
10.4
通讯作者：
Kannio, A
中科院分区：
文献类型：
--
作者：
HusgafvelPursiainen, K;Kannio, A
我们在这里报告的汇编p53基因突变的结果，从两个吸烟相关的癌症，肺癌和膀胱癌。这两种癌症的总体突变频率相对相似-肺癌为50%，膀胱癌为40%。来自肺癌和膀胱癌的汇编数据表明，在两个癌症组中，不吸烟者、前吸烟者和当前吸烟者中p53突变患者的比例依次增加。加在一起，超过一半（肺癌和膀胱癌分别为55%和56%）的患者继续吸烟（CS），低于40%（38%和38%）以前戒烟的人（大于或等于1年或大于或等于5年）临床诊断（ES），而在不吸烟者（NS）中，p53基因突变率低于30%（25%和29%）。然而，三个吸烟组之间的突变频率差异没有达到统计学意义（肺癌-CS vs ES：比值比[OR]=2.0，95% CI 0.7-5.4; CS vs NS：OR=3.7，95% CI 0.4-37;膀胱癌-CS vs ES：OR=2.1，95% CI 0.6-7.9; CS vs NS：OR=3.1，95% CI 0.7-13）。鸟嘌呤到胸腺嘧啶颠换是肺癌中最常见的类型，其次是鸟嘌呤到腺嘌呤的转换。相反，在膀胱癌中，胞嘧啶-鸟嘌呤二核苷酸位点的G：C至A：T转变是最常检测到的碱基替换。对p53突变数据的分析表明，除了终生累积暴露于香烟烟雾之外，在疾病临床表现之前数年的吸烟也可能影响p53突变的发生率。突变谱的差异似乎支持这样的观点，即与肺癌相比，膀胱癌中来自香烟烟雾暴露的主要遗传毒性剂可能是不同的，正如先前DNA加合物研究所表明的那样。
We report here a compilation of p53 mutation results from two smoking-related cancers, lung cancer and bladder cancer. The overall mutation frequencies reported for these two types of cancer were relatively similar-50% in lung cancer and 40% in bladder cancer. The compiled data from lung cancer and bladder cancer suggest an increasing proportion of patients with p53 mutations in nonsmokers, former smokers, and current smokers, in that order, in both cancer groups. Taken together, more than half (55% and 56% for lung cancer and bladder cancer, respectively) of the patients who continued smoking (CS), less than 40% (38% and 38%) of those who had stopped smoking before (greater than or equal to 1 or greater than or equal to 5 years) clinical diagnosis (ES), and less than 30% (25% and 29%) of those who were nonsmokers (NS) had a p53 mutation. The differences seen in the mutation frequencies between the three smoking groups did not, however, reach statistical significance (lung cancer-CS vs ES: odds ratio [OR]=2.0, 95% CI 0.7-5.4; CS vs NS: OR=3.7, 95% CI 0.4-37; bladder cancer-CS vs ES: OR=2.1, 95% CI 0.6-7.9; CS vs NS: OR=3.1, 95% CI 0.7-13). Guanine to thymine transversions were the most common type in lung cancer followed by guanine to adenine transitions. In bladder cancer, on the contrary, G:C to A:T transitions at cytosine-guanine dinucleotide sites were the most frequently detected base substitutions. Analysis of the compiled p53 mutation data suggests that, in addition to lifetime cumulative exposure to cigarette smoke, also slopping smoking for years prior to clinical manifestation of the disease may affect the incidence of p53 mutations. The differences in the mutation profiles appear to support the view that the main genotoxic agents from cigarette smoke exposure may be different in bladder cancer as compared to lung cancer, as suggested previously by DNA adduct studies.