Szymanowska Amelia, Jassem Ewa, Dziadziuszko Rafał, Borg Ake, Limon Janusz, Kobierska-Gulida Grazyna, Rzyman Witold, Jassem Jacek
Department of Allergology, Medical University of Gdansk, Gdansk, Poland.
Lung Cancer. 2006 Apr;52(1):9-14. doi: 10.1016/j.lungcan.2005.12.007. Epub 2006 Feb 24.
The aim of this study was to assess whether the TP53 Arg72Pro polymorphism is associated with an increased risk of non-small cell lung cancer (NSCLC). Additionally, in NSCLC patients, we investigated a potential association between this polymorphism and somatic TP53 gene mutations in tumour cells. The study group included 240 NSCLC patients who underwent curative pulmonary resection. The control group (576 healthy subjects) was matched for sex and cigarette smoking. TP53 Arg72Pro polymorphism was determined by denaturing high-performance liquid chromatography. Tumours from 157 NSCLC patients were analysed for mutation in TP53 exons 5-8 by single strand conformation polymorphism, followed by sequencing of samples with different band pattern. Tumours from the remaining 83 patients were subjected to a direct sequencing of TP53 exons 5-8. The proportion of Pro homo/heterozygotes versus Arg homozygotes was significantly higher in NSCLC patients (54%) than in controls (46%, p = 0.034). The crude odds ratio for NSCLC development in Pro72 allele carriers was 1.39 (95% CI: 1.03-1.88). When adjusted for sex, age and smoking status in the multivariate logistic regression model, odds ratio for NSCLC development was 1.28 (95% CI: 0.91-1.80). Somatic TP53 mutations were found in 62 out of 240 NSCLC patients (26%), more frequently in Pro carriers (31%) than in Arg homozygotes (20%, p = 0.06). These results indicate that the TP53 codon 72 Pro allele may increase the risk of NSCLC. Additionally, the correlation between Pro72 and somatic TP53 mutations suggests that Pro72 allele carriers may be predisposed to tumour development along a p53 associated form of NSCLC, a finding that warrants further investigations.
本研究的目的是评估TP53基因第72位密码子的精氨酸（Arg）/脯氨酸（Pro）多态性是否与非小细胞肺癌（NSCLC）风险增加相关。此外，在NSCLC患者中，我们研究了这种多态性与肿瘤细胞中TP53基因体细胞突变之间的潜在关联。研究组包括240例行根治性肺切除术的NSCLC患者。对照组（576名健康受试者）在性别和吸烟情况方面进行了匹配。采用变性高效液相色谱法测定TP53基因第72位密码子的Arg/Pro多态性。对157例NSCLC患者的肿瘤组织进行单链构象多态性分析，检测TP53基因外显子5 - 8的突变情况，随后对具有不同条带模式的样本进行测序。其余83例患者的肿瘤组织则直接进行TP53基因外显子5 - 8的测序。NSCLC患者中Pro纯合子/杂合子与Arg纯合子的比例（54%）显著高于对照组（46%，p = 0.034）。Pro72等位基因携带者发生NSCLC的粗比值比为1.39（95%可信区间：1.03 - 1.88）。在多因素逻辑回归模型中，对性别、年龄和吸烟状况进行校正后，发生NSCLC的比值比为1.28（95%可信区间：0.91 - 1.80）。240例NSCLC患者中有62例（26%）检测到TP53基因体细胞突变，Pro等位基因携带者中的突变频率（31%）高于Arg纯合子（20%，p = 0.06）。这些结果表明，TP53基因第72位密码子的Pro等位基因可能增加NSCLC的发病风险。此外，Pro72与TP53基因体细胞突变之间的相关性表明，Pro72等位基因携带者可能易患与p53相关的NSCLC肿瘤发展形式，这一发现值得进一步研究。
