title: The XbaI G>T polymorphism of the glucose transporter 1 gene modulates 18F-FDG uptake and tumor aggressiveness in breast cancer.
abstract: We investigated the relevance of single-nucleotide polymorphisms (SNPs) in the glucose transporter 1 (GLUT1) gene to the uptake of (18)F-FDG and tumor aggressiveness in breast cancer.
  
  
  METHODS
  In 52 individuals with breast cancer, a diagnostic PET/CT scan was obtained, and the standardized uptake value was determined as a measure of (18)F-FDG uptake using a region-of-interest technique. Three GLUT1 SNPs (XbaI G>T, HpyCH4V A>T, and HaeIII T>C) were investigated in genomic DNA that was isolated from the paraffin-embedded specimens of all patients. Tumors were typed and graded according to the World Health Organization classifications.
  
  
  RESULTS
  The GG genotype of the XbaI G>T SNP was associated with increased tumor uptake of (18)F-FDG, with a mean standardized uptake value of 11.7 (TT/GT genotypes, 5.9; P = 0.03). Furthermore, the GG genotype was positively related to enhanced tumor proliferation (mitotic count, P = 0.01). In line with this finding, the GG genotype was absent in grade 1 carcinomas and increasingly prevalent in tumors with higher malignancy (grade 2, 28.0%; grade 3, 50%; P = 0.04).
  
  
  CONCLUSIONS
  This study found that the XbaI G>T SNP of the GLUT1 gene is associated with an increased (18)F-FDG uptake and a more advanced tumor grade or growth in breast cancer. Thus, this genetic variant might favor aggressive phenotypes by modulating the efficiency of cancer cells to recruit glucose and escalate growth rate, suggesting the XbaI G>T SNP as a proliferation-related prognostic factor.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. florian.grabellus@uk-essen.de
authors.forename: Florian
authors.initials: F
authors.lastname: Grabellus
authors.forename: Sien-Yi
authors.initials: SY
authors.lastname: Sheu
authors.forename: Hagen S
authors.initials: HS
authors.lastname: Bachmann
authors.forename: Nils
authors.initials: N
authors.lastname: Lehmann
authors.forename: Friedrich
authors.initials: F
authors.lastname: Otterbach
authors.forename: Till A
authors.initials: TA
authors.lastname: Heusner
authors.forename: Gerald
authors.initials: G
authors.lastname: Antoch
authors.forename: Andreas
authors.initials: A
authors.lastname: Bockisch
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Schmid
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Stahl
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D005260:Female; D019788:Fluorodeoxyglucose F18; D005838:Genotype; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051272:Glucose Transporter Type 1; D019275:Radiopharmaceuticals; C495677:SLC2A1 protein, human; D019788:Fluorodeoxyglucose F18