林州居民食管癌p53基因突变谱分析与不同地区食管癌和其他类型肿瘤的比较

Analysis of p53 mutational spectra of esophageal squamous cell carcinomas from Linzhou, comparison with esophageal and other cancers from other areas

目的 分析河南省林州市与其他地区食管癌前病变和鳞状细胞癌 p5 3突变谱 ,探讨食管癌变的发病因素。方法 采用生物信息学和MonteCarlo方法 ,依据IARCp5 3突变数据库、Curic研究院 p5 3突变数据库和郑州大学医学院癌症研究所实验室的资料 ,用FileMarkPro3 .0软件系统建立局部资料库进行分析。结果 林州食管癌高发区食管鳞癌碱基替换的发生率低于其他地区食管鳞癌的发生率 ( 3 2 .8%vs 3 9.8% ) ,但CpG位点G∶C→A∶T的发生率高于其他地区食管癌 ( 2 9.6%vs16.4% )。林州食管癌突变位点具有明显的特征 ,主要发生在 2 73 (占所有错义突变的 11.3 % )、175( 9.7% )、15 9( 6.5 % )和 2 82 ( 6.5 % )位密码子的CpG位点上。林州地区食管鳞癌 p5 3突变与其他地区食管鳞癌以及头颈部鳞癌 p5 3突变相比 ,差异有显著性 ( P =0 .0 2 )。结论 林州食管癌 p5 3突变具有内、外源致癌原所致突变的特征 ,提示慢性炎症、饮食习惯和接触致癌原 。

Objective To study the etiological clues involved (in esophageal cancer in Linzhou, Henan, a high-incidence area for esophageal cancer) by analyzing p53 mutational spectrum from esophageal precancerous and cancerous lesions.Methods Using bolt bioinformatic and Monte Carlo methods to analyze p53 mutation spectra from 'The IARC Database of Somatic p53 Mutations in Human Tumors and Cell Lines', 'p53 Database at Institute Curic' and to establish a local database based on these data using the FileMark Pro 3.0 software to allow fast and off-line analysis on a PC from the authors' laboratory. Results We found that esophageal squamous cell carcinomas from Linzhou had a lower prevalence of base substitutions associated with strand bias than those from other areas ( 32.8% vs 39.8%). However, a higher prevalence of G∶ C→ A∶T transitions at CpG site ( 29.6% vs 16.4%) was found. Esophageal squamous cell carcinomas from Linzhou displayed a distinctive profile of mutation hotspots, including codons 273 (covers 11.3% of all missense mutations), 175 ( 9.7%),158 ( 9.7%), 159 ( 6.5%) and 282 ( 6.5%), all of which were at the CpG site. Statistical analysis showed that the p53 mutation profiles between esophageal squamous cell carcinomas from Linzhou and those from other areas were different ( P= 0.02). The p53 mutation profiles of esophageal squamous cell carcinomas from Linzhou and from other areas were also different from cancer of the head and neck.Conclusion Data showed that the p53 mutational spectrum of esophageal squamous cell carcinomas from Linzhou baring the characteristics of those caused both by endogenous and exogenous mutagenic agents, suggesting the potential involvement of chronic inflammation, unique dietary habits and carcinogen exposure in the pathogenesis of esophageal squamous cell carcinoma in Linzhou.