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膀胱癌的分子与流行病学研究:p53 突变、吸烟与石棉职业暴露

A molecular and epidemiological study on bladder cancer: p53 mutations, tobacco smoking, and occupational exposure to asbestos.

作者信息

Kannio A, Ridanpää M, Koskinen H, Partanen T, Anttila S, Collan Y, Hietanen E, Vainio H, Husgafvel-Pursiainen K

机构信息

Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.

出版信息

Cancer Epidemiol Biomarkers Prev. 1996 Jan;5(1):33-9.

PMID:8770464
Abstract

In this study, we found an unexpected association (crude odds ratio = 2.8; 95% confidence interval = 0.9-8.4) between definite work-related exposure to asbestos and carcinoma of the urinary bladder in a small group of patients (n = 28) initially recruited as referents for an epidemiological feasibility study on the occupational causes of lung cancer. We extended the study by using molecular methods to examine mutations in the p53 tumor suppressor gene in the same cases of bladder cancers. The same number of archival samples of transitional cell carcinoma, mainly of grade 3, were added to the analysis. We failed to show any association between occupational exposure to asbestos and p53 mutations among bladder cancer patients. We observed an increasing occurrence of p53 mutations in nonsmokers (5 of 17, 29%), former smokers (8 of 21, 38%), and current smokers (9 of 16, 56%) in that order; however, this was not statistically significant. The most prevalent type of mutation was G:C to A:T transition. Tumor grade was not associated with the frequency of mutations, but the higher stage (T3-T4) tumors appeared to have mutations more frequently than did the less invasive tumors (T1-T2).

摘要

在本研究中,我们在一小群最初作为肺癌职业病因流行病学可行性研究对照招募的患者(n = 28)中发现,明确的与工作相关的石棉暴露与膀胱癌之间存在意外关联(粗比值比 = 2.8;95%置信区间 = 0.9 - 8.4)。我们通过分子方法扩展了该研究,以检测同一组膀胱癌病例中p53肿瘤抑制基因的突变情况。分析中加入了相同数量的主要为3级的移行细胞癌存档样本。我们未能在膀胱癌患者中显示出职业性石棉暴露与p53突变之间存在任何关联。我们观察到,不吸烟者(17例中的5例,29%)、既往吸烟者(21例中的8例,38%)和当前吸烟者(16例中的9例,56%)中p53突变的发生率依次增加;然而,这在统计学上并不显著。最常见的突变类型是G:C到A:T的转换。肿瘤分级与突变频率无关,但较高分期(T3 - T4)的肿瘤似乎比侵袭性较小的肿瘤(T1 - T2)更频繁地出现突变。

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A molecular and epidemiological study on bladder cancer: p53 mutations, tobacco smoking, and occupational exposure to asbestos.膀胱癌的分子与流行病学研究:p53 突变、吸烟与石棉职业暴露
Cancer Epidemiol Biomarkers Prev. 1996 Jan;5(1):33-9.
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Oncol Rep. 2010 Jul;24(1):257-62. doi: 10.3892/or_00000854.
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The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability.人类骨肉瘤中p53突变的存在与高水平的基因组不稳定性相关。
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11547-52. doi: 10.1073/pnas.1934852100. Epub 2003 Sep 12.
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LKB1 somatic mutations in sporadic tumors.
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Overcoming cellular senescence in human cancer pathogenesis.克服人类癌症发病机制中的细胞衰老
Genes Dev. 1998 Jan 15;12(2):163-74. doi: 10.1101/gad.12.2.163.
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Cigarette smoking and p53 mutations in lung cancer and bladder cancer.肺癌和膀胱癌中的吸烟与p53突变
Environ Health Perspect. 1996 May;104 Suppl 3(Suppl 3):553-6. doi: 10.1289/ehp.96104s3553.