Diverse prognostic value of the GTn promoter polymorphism in squamous cell and adeno carcinoma of the esophageus

Abstract

The basal transcription of heme-oxygenase-1 (HO-1) regulation is dependent upon a GT repeat germ line polymorphism (GTn) in the promoter of the HO-1 gene. We determined the prognostic value of HO-1 promoter polymorphism on the natural postoperative course of complete resected esophageal cancer (EC). Genomic DNA from 297 patients was amplified by PCR and sequenced. The results were correlated with clinico-pathological parameters, disseminated tumor cells in bone marrow (DTC) and clinical outcome. Depending on short allele with <25 and long allele with ≥25 GTn repeats three genotypes (SS, SL and LL) were defined. A diverse role of GTn was evident in squamous cell carcinoma (SCC) and adenocarcinoma (AC). In SCC the SS genotype presented less advanced tumors with lower rate DTC in bone marrow and relapse compared to L-allele carriers. In contrast AC patients with the SS genotype displayed a complete opposing tumor characteristic. The disease-free (DFS) and overall survival (OS) in SCC patients was markedly reduced in LL genotypes (P < 0.001). In AC contrarily the SS genotype patients displayed the worst DFS and OS (P < 0.001). GTn is a strong prognostic factor with diverse prognostic value for recurrence and survival in AC and SCC.

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