P53 alterations in bladder tumors from arsenic and tobacco exposed patients
P53 alterations in bladder tumors from arsenic and tobacco exposed patients
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DOI：
10.1093/carcin/bgg136
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发表时间：
2003-11-01
期刊：
影响因子：
4.7
通讯作者：
Waldman, FM
中科院分区：
文献类型：
--
作者：
Moore, LE;Smith, AH;Waldman, FM
以往的研究表明，烟草和砷暴露是膀胱癌的危险因素。进行了一项病例-病例研究，比较了147例南美患者烟草和砷暴露膀胱肿瘤中的p53突变。收集居住史和生活方式因素的信息。p53突变和蛋白表达的患病率与肿瘤分期、分级、患者年龄、性别、烟草和砷暴露有关。吸烟者被分为曾经吸烟者/从不吸烟者，并按暴露包年（0，1-20，>20）分组。根据饮用水中砷浓度最高的五年的平均值，将患者分为四个砷暴露类别：第1组，不可检测到300 μ g/l（n=30）。p53突变和P53免疫阳性的肿瘤样本的比例随着分期和分级的增加而增加，但与砷暴露或吸烟无关。含有突变转换的肿瘤的患病率随着肿瘤分期（从14到52%，P趋势=0.005）和级别（从11到48%，P趋势=0.004）而显著增加，并且吸烟者高于非吸烟者（分别为34%和18%，P=0.10）。随着吸烟包年数的增加，观察到了增加的趋势（P=0.09）。吸烟者和非吸烟者肿瘤中的大多数突变是G->A转换，然而，在吸烟者中观察到CpG位点的G->A转换偏好（P=0.07，双尾），并且随着包年暴露观察到正趋势（P=0.04）。12%的吸烟者的肿瘤在密码子273处发现热点，但在从不吸烟者中未观察到（P=0.05），并且随着烟草暴露包年的增加观察到正趋势（P=0.001）。无论是分期还是分级都没有表现出对CpG位点突变的偏好，这表明这些变化可能是癌发生过程中的早期凋亡相关事件，与肿瘤进展无关。砷暴露与p53突变或P53免疫阳性的患病率增加无关，也没有证据表明砷和吸烟与这些结果变量之间存在相互作用。
Previous studies demonstrated that tobacco and arsenic exposure are risk factors for bladder cancer. A case-case study was conducted to compare p53 mutations in 147 bladder tumors from South American patients by tobacco and arsenic exposure. Information on residential history and lifestyle factors was collected. The prevalence of p53 mutations and protein expression was examined in relation to tumor stage, grade, patient age, gender, tobacco and arsenic exposure. Smokers were grouped as ever/never smokers and by pack years of exposure (0, 1-20, >20). Patients were also grouped into four arsenic exposure categories based on the average of the five highest years arsenic concentration in their drinking water: group 1, non-detectable to 300 mug/l (n=30). The proportion of tumor samples with p53 mutations and P53 immunopositivity increased strongly with both stage and grade, but not with arsenic exposure or smoking. The prevalence of tumors containing mutational transitions increased markedly with tumor stage (from 14 to 52%, P-trend=0.005) and grade (from 11 to 48%, P-trend=0.004) and was higher in smokers than in non-smokers (34 versus 18%, respectively, P=0.10). An increasing trend was observed with pack years of smoking (P=0.09). The majority of mutations in tumors from both smokers and non-smokers were G-->A transitions, however, in smokers a preference for G-->A transitions at CpG sites was observed (P=0.07, two-tailed) and a positive trend was observed with pack years of exposure (P=0.04). A hotspot was found at codon 273 in 12% of the tumors from smokers but was not observed in never smokers (P=0.05) and a positive trend was observed with pack years of tobacco exposure (P=0.001). Neither stage nor grade demonstrated a preference for CpG site mutation, suggesting that these changes may be early exposure-related events in carcinogenesis and are not related to tumor progression. Arsenic exposure was not associated with an increased prevalence of p53 mutation or P53 immunopositivity and there was no evidence of interaction between arsenic and smoking with these outcome variables.