title: Glucose transporter polymorphisms are associated with clear-cell renal carcinoma.
abstract: Clear-cell renal cell carcinoma (CCRCC) is identified by abundant glycogen-rich cytoplasm, due to the aberrant influx and storage of glucose. The objective was to investigate the frequency of polymorphisms of the facilitative glucose transporter (GLUT1). GLUT1 is a downstream target of Hypoxia-inducible factor (HIF-1alpha), a mediator of hypoxia-controlled angiogenesis. In this study, we examine the allelic frequency of polymorphisms in the promoter and the second intron of the GLUT1 gene. Genomic DNA was extracted from normal tissue of 92 patients undergoing nephrectomy for CCRCC, and 99 normal cord blood DNA samples were used to provide control frequencies. The regions of DNA encompassing the polymorphisms were amplified and digested with appropriate endonuclases. The products were separated and viewed by gel electrophoresis. There was a highly significant decrease in the A-2841 genotype (P=0.0004) in the promoter region of those patients with CCRCC compared to the control population. There was also a significant decrease in the T+22999 allele in the intron 2 of those patents with CCRCC (P=0.004) compared to the same control population. This study suggests that GLUT1 is one of a number of genes that may increase susceptibility to developing CCRCC.
authors.affiliation: Molecular Medicine Research Group, Peninsula Medical School, Institute of Biomedical Sciences, Peninsula Medical School Headquarters, Derriford, Plymouth PL6 8BU, United Kingdom. Toby.page@pms.ac.uk
authors.forename: Tobias
authors.initials: T
authors.lastname: Page
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Hodgkinson
authors.forename: Martin
authors.initials: M
authors.lastname: Ollerenshaw
authors.forename: John C
authors.initials: JC
authors.lastname: Hammonds
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Demaine
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D020022:Genetic Predisposition to Disease; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D017931:DNA Primers; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human