Analysis of a promoter polymorphism of the GLUT1 gene in patients with hepatocellular carcinoma

The glucose transporter isoform 1 (GLUT1) is a key rate-limiting factor in the transport and metabolism of glucose in cancer cells. Recently, we found that Glut1 expression is increased in hepatocellular carcinoma (HCC) and promotes tumorigenesis. Hypoxia further increased GLUT1 expression in HCC cells, and this induction was dependent on the activation of the transcription factor hypoxia-inducible factor (HIF)-1alpha.

The promoter region of the GLUT1 gene harbours a single nucleotide polymorphism (SNP) closely positioned to a putative HIF-1alpha binding site, and recently, it has been shown that the frequency of the A-2841 genotype was significantly increased in patients with renal cell carcinoma.

The aim of this study was to analyze this SNP in HCC patients.

Methods and Results: The A -2841T SNP was analyzed in genomic DNA isolated from tumorous as well as non-tumorous hepatic tissue by PCR and subsequent restriction fragment length polymorphism (RFLP) analysis. Genotype distribution did not differ significantly between HCC patients (n=100; AA: 61%; AT 34% and TT: 5%) and healthy controls (n=127; AA: 50%; AT 41% and TT: 9%). Analysis of genomic DNA isolated from tumorous as well as non-tumorous hepatic tissue revealed identical results. Further, carriers and non-carriers of the A-allele had similar GLUT1 mRNA levels in both cancerous as well as non-cancerous hepatic tissue as assessed by quantitative PCR.

Conclusion: The SNP Rs710218 does not affect hepatic GLUT1 expression and is not associated with a higher risk for HCC.