Abstract
We have previously cloned and identified a novel esophageal cancer related gene 2 (ECRG2; GenBank Accession Number AF268198), which is down-regulated in esophageal squamous cell carcinoma (ESCC) and involved in the induction of the apoptosis in esophageal cancer cell lines. In the present study, we have found a short tandem repeat (STR) polymorphism in the noncoding region of the exon 4 of the ECRG2 gene by using PCR-denaturing high-performance liquid chromatography (DHPLC). Three STR genotypes, TCA3/TCA3, TCA3/TCA4 and TCA4/TCA4 were revealed and confirmed by DNA sequencing analysis. A total of 661 objects including 228 patients with ESCC and 373 normal controls were analyzed to investigate the impact of this ECRG2 STR polymorphism on risk of ESCC in case-control studies. Genotypes were determined in 231 controls and 162 cases from Beijing, which is a low risk area of ESCC, and in 142 controls and 126 cases from Linxian, a well-known high-risk area of ESCC. In both of the Beijing and Linxian population, subjects who carried the TCA3/TCA3 genotype were at an increased risk of ESCC compared to those carrying the TCA4/TCA4 genotype, with the adjusted odds ratios (ORs) being 2.05 [95% confidence interval (CI), 1.02-4.06] for the subjects from Beijing and 4.40 (95% CI, 1.93-10.01) for the subjects from Linxian. Furthermore, comparison of the genotype distributions among other cancer sites might suggest that risk of the ECRG2 STR polymorphism might be specific to the esophagus. These findings indicate for the first time that the ECRG2 STR is a genetic susceptibility factor for ESCC and the TCA3/TCA3 allele might play a role in the development of this cancer.
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