The XbaI G>T polymorphism of the glucose transporter 1 gene modulates 18F-FDG uptake and tumor aggressiveness in breast cancer.
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.
Grabellus
Florian
F
Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. florian.grabellus@uk-essen.de
Sheu
Sien-Yi
SY
Bachmann
Hagen S
HS
Lehmann
Nils
N
Otterbach
Friedrich
F
Heusner
Till A
TA
Antoch
Gerald
G
Bockisch
Andreas
A
Kimmig
Rainer
R
Schmid
Kurt W
KW
Stahl
Alexander R
AR
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
D051272:Glucose Transporter Type 1; D019275:Radiopharmaceuticals; C495677:SLC2A1 protein, human; D019788:Fluorodeoxyglucose F18