Relationship between TP53 tumour suppressor gene mutations and smoking-related bulky DNA adducts in a lung cancer study population from Hungary
Relationship between TP53 tumour suppressor gene mutations and smoking-related bulky DNA adducts in a lung cancer study population from Hungary
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DOI：
10.1093/mutage/gep031
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发表时间：
2009-11-01
期刊：
影响因子：
2.7
通讯作者：
Schoket, Bernadette
中科院分区：
文献类型：
--
作者：
Anna, Livia;Holmila, Reetta;Schoket, Bernadette
匈牙利是世界上男性肺癌发病率最高的国家之一，女性肺癌发病率也很高，原因尚不清楚。本研究的目的是探讨匈牙利肺癌DNA损伤和TP 53基因突变的特点。研究了来自104例肺癌患者（男性和女性）肺切除术的组织样本，这些患者因非小细胞肺癌，特别是原发性鳞状细胞癌或腺癌而接受手术。在这些病例中，37%在手术前吸烟，24%在手术前1年内戒烟，26%在手术前1年以上戒烟，13%从不吸烟。采用变性梯度凝胶电泳、自动毛细管电泳单链构象多态性分析和测序技术检测TP 53基因突变。在非肿瘤肺组织中通过P-32-后标记测定大体积DNA加合物水平。总的来说，45%（47/104）的病例携带TP 53突变。TP 53突变的患病率与吸烟持续时间、肿瘤组织学和性别在统计学上显著相关。吸烟者的大体积加合物水平大约是前吸烟者和从不吸烟者合并组的两倍（10.9 +/- 6.5 vs 5.5 +/- 3.4加合物/10（8）个核苷酸）。G -> T颠换（8/43; 19%）仅在吸烟者中检测到。我们首次证明，大多数G -> T颠换的携带者在其非肿瘤肺组织中也具有高水平的大体积DNA加合物。我们的研究为肺癌患者的肺中同时发生的高负荷分子改变提供了证据。
Lung cancer rate in Hungary is one of the highest in the world among men and also very high among women, for reasons not clearly understood yet. The aim of the study was to explore characteristics of DNA damage and TP53 gene mutations in lung cancer from Hungary. Tissue samples from 104 lung resections for lung cancer patients, both men and women, operated on for non-small cell lung cancer, specifically, primary squamous cell carcinoma or adenocarcinoma were studied. Of the cases, 37% smoked up to the surgery, 24% stopped smoking within 1 year before the surgery, 26% stopped smoking more than a year before the surgery and 13% never smoked. TP53 mutations were detected by denaturant gradient gel electrophoresis, automated capillary electrophoresis single-strand conformation polymorphism and sequencing. Bulky DNA adduct levels were determined by P-32-post-labelling in non-tumorous lung tissue. In total, 45% (47/104) of the cases carried TP53 mutation. The prevalence of TP53 mutations was statistically significantly associated with duration of smoking, tumour histology and gender. Smokers had approximately twice as high bulky adduct level as the combined group of former- and never-smokers (10.9 +/- 6.5 versus 5.5 +/- 3.4 adducts/10(8) nucleotides). The common base change G -> T transversion (8/43; 19%) was detected exclusively in smokers. For the first time, we demonstrate that most carriers of G -> T transversions had also a high level of bulky DNA adducts in their non-tumourous lung tissue. Our study provides evidence for a high burden of molecular alterations occurring concurrently in the lung of lung cancer patients.