西安和林州市食管癌比较分子流行病学研究

A COMPARATIVE MOLECULAR EPIDEMIOLOGICAL STUDY ON ESOPHAGEAL CANCER BETWEEN XI ,AN AND LINZHOU

目的：通过西安市和林州市食管癌ｐ５３ 基因高表达率、危险因素及其第五外显子突变谱和突变模式的比较研究，初步探讨两地食管癌分子病因的异同。方法：分别在西安市和林州市收集食管癌病例１３７ 例、６７ 例及相应对照，调查其相关既往史；对癌组织以免疫组化和 Ｐ Ｃ Ｒ 直接测序方法检测 Ｐ５３ 蛋白和ｐ５３ 基因第五外显子突变情况；危险因素分析以单因素分析和多因素 Ｌｏｇｉｓｔｉｃ 回归模型进行。结果：西安市食管癌发病及 Ｐ５３ 高表达与吸烟和食管癌家族史有关，而林州市则与食用酸菜和食管癌家族史有关。西安市病例ｐ５３ 第五外显子突变谱相对集中（１５７ 、１５９ 密码子为主） ， Ｇ→ Ｔ 颠换较多见（５／１０） ；而林州市病例突变位点较分散。结论：ｐ５３ 突变和食管癌家族史是两地食管癌的共同病因，但两地ｐ５３ 基因突变的环境因素、突变谱和模式差异较大，表明其分子癌变机理也可能不同。

Objective:By the comparative study of the risk factors of esophageal cancer(EC) and it ,s p53 gene overexpression, the mutation spectrum and pattern of exon 5 of p53 gene between Xi , an and Linzhou, to explore the heterogenecity of molecular etiology of EC between the two cities. Methods: EC cases in Xi ,an(N=137) and Linzhou (N=67) with related controls and their previous related history were collected respectively. Immunohistochemistry and PCR-direct sequencing were used to detect the p53 gene overexpression and mutation spectrum and pattern of exon 5 in EC tissues. The risk factors of EC and p53 gene overexpression were studied by single variable and multivariable Logistic regresion analysis. Results: In Xi ,an the EC morbidity and p53 gene overexpression were closely related with smoking and family history of EC(FHEC), while in Linzhou they were related with consumption of pickled vegetables and FHEC. In Xi ,an EC cases the mutation spectrums of exon 5 were relatively concentrated( mainly codon 157、159), and the G→T transversion was most prevalent(5/10); but in Linzhou EC cases they were dispersed. Conclusion: p53 gene mutation and FHEC were the common etiological factors in Xi ,an and Linzhou, but the environmental factors related with p53 gene overexpression and the mutation spectrum of exon 5 were different, and those indicated that the mechanism of molecular carcinogenesis may be different between the two cities.