CDH1基因Exon1非编码区插入/缺失多态性与膀胱移行细胞癌易感性的关系

Relationship between an insertion/deletion polymorphism in noncoding region of exon1 of CDH1 Gene and susceptibility of transitional cell carcinoma of the bladder

目的:探讨上皮钙粘素(E-cadherin,CDH1)基因Exon1非编码区234bp位点插入/缺失多态性与膀胱移行细胞癌(TCCB)生物学行为之间的关系。方法:从TCCB组180例,对照组健康人110例的血液中提取人基因组DNA,PCR获取包含CDH1基因启动子近侧序列-160位点和Exon1的DNA片段,DNA测序方法测得上述DNA片断的基因序列。选择χ2检验进行统计学分析,Woolf法计算OR值(odd sratio,OR)和95%CI。结果:CDH1基因Exon1非编码区234bp位点插入片断碱基序列为5'-CCGTGCCCCAGCC-3',其插入/缺失多态性基因型分为插入\插入纯合子(I/I)、缺失\缺失纯合子(D/D)和插入\重复插入杂合子(I/2I)三种。TCCB组该位点I/2I基因型频率(0.54)高于对照组(0.35)(P<0.01),提示I/2I基因型患TCCB风险较高(OR=2.15,95%CI1.32～3.52)。结论:CDH1基因Exon1非编码区234bp位点2I等位基因频率与膀胱移行细胞癌的发生密切相关。-160A/A-234I/2I基因型与膀胱移行细胞癌的发生密切相关。

Objective：To investigate whether an Insertion/Deletion polymorphism in noncoding region of Exon 1 of CDH1 gene was associated with susceptibility of TCCB. Methods：A hospital-based case-control study was performed on 180 patients with TCCB and 110 normal controls. Genomic DNA was extracted from blood samples of the subjects. DNA fragments including -160 bp position and Exonl were obtained by PCR. Genotypes were determined using DNA sequencing. Significance of difference was determined by Chi square test. Calculation of OR and 95 % CI was performed by Woolf method. Results： A 5-CCGTGCCCCAGCC-3 Insertion/Deletion polymorphism in 234 position of Exonl of CDH1 gene was detected by DNA sequencing technique. Its genotype was homozygous for 5-CCGTGCCCCAGCC-3 allele insertion（I/I）, homozygous for 5-CCGTGCCCCAGCC-3 allele deletion（D/D） and heterozygous for 5-CCGTGCCCCAGCC-3 allele insertion/repeat insertion（I/2I）, respectively. The 21 allele frequencies were significantly higher in TCCB than in normal controls（ P 〈0.05）, and 1/21 carriers had a higher relative risk of TCCB （OR= 2.15, 95 % CI1. 32-3. 52） compared to I/I carriers. Conclusions： The 234 bp 21 allele frequency in noncoding region of Exonl of CDH1 gene as well as - 160A/A-234I/2I genotype were closed related to susceptibility of TCCB.