Abstract
BackgroundPositron emission tomography imaging of lung cancers with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose is a non-invasive diagnostic, and prognostic tool that measures tumor metabolism. We have analyzed the effect of solute carrier family 2 (facilitated glucose transporter), member 1 polymorphisms on 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-uptake with a combination of polymorphisms of hypoxia-inducible factor 1 alpha, apurinic/apyimidinic endonuclease, and vascular endothelial growth factor A in a hypoxia-related pathway.MethodsWe investigated the association between solute carrier family 2 (facilitated glucose transporter), member 1 -2841A>T, hypoxia-inducible factor 1 alpha Pro582Ser, Ala588Thr, apurinic/apyimidinic endonuclease Asp148Glu, or vascular endothelial growth factor A +936C>T and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-uptake among 154 patients with non-small-cell lung cancer.ResultsThe solute carrier family 2 (facilitated glucose transporter), member 1 -2841A>T polymorphism was significantly associated with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-uptake in combination with the apurinic/apyimidinic endonuclease Asp148Glu (T>G) polymorphism in the squamous cell type of non-small-cell lung cancer. The solute carrier family 2 (facilitated glucose transporter), member 1 TT genotype had a higher maximum standardized uptake values than the AA + AT genotype when the apurinic/apyimidinic endonuclease genotype was TT (mean maximum standardized uptake values, 12.47 ± 1.33 versus 8.46 ± 2.90, respectively; P = 0.028). The mean maximum standardized uptake values were not statistically different with respect to vascular endothelial growth factor A and hypoxia-inducible factor 1 alpha polymorphisms.ConclusionA glucose transporter gene polymorphism was shown to be statistically associated with glucose-uptake when the apurinic/apyimidinic endonuclease genotype is TT in patients with the squamous cell type of non-small-cell lung cancer. Our findings suggest that a newly developed tracer for positron emission tomography could be affected by genetic polymorphisms.
Highlights
Positron emission tomography (PET) imaging of malignant tumors with 2-[fluorine-18]-fluoro-2-deoxy-D-glu-called glucose transporter type 1, GLUT1) gene is the primary glucose transporter gene in human lung cancer [2].Hypoxia-inducible factor 1a (HIF-1a) controls oxygen delivery via angiogenesis and metabolic adaptation to hypoxia via glycolysis [3]
The T variant, which is linked to lower VEGFA levels, has been associated with colon cancer [10] and low FDG uptake [11]. These findings suggest a potential role of the VEGFA 936C>T polymorphism for the variability of FDG uptake in tumor tissues
The inclusion criteria were as follows: (1) patients had a pathologically-confirmed diagnosis of non-small cell lung cancer (NSCLC) (2) and peripheral blood lymphocytes and FDG-PET images were available for analysis
Summary
Positron emission tomography (PET) imaging of malignant tumors with 2-[fluorine-18]-fluoro-2-deoxy-D-glu-. Hypoxia-inducible factor 1a (HIF-1a) controls oxygen delivery via angiogenesis and metabolic adaptation to hypoxia via glycolysis [3]. A large number of clinicopathologic studies have confirmed that unlike mature normal tissues, HIF-1a is overexpressed in the cytoplasm and nuclei of 40%-80% of human carcinomas, including lung, breast, head and neck, endometrial cancers, melanomas, and sarcomas [5,6]. Fu et al [7] and Koukourakis et al [8] showed that a HIF1A gene polymorphism affected HIF-1a protein expression. Positron emission tomography imaging of lung cancers with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose is a non-invasive diagnostic, and prognostic tool that measures tumor metabolism. We have analyzed the effect of solute carrier family 2 (facilitated glucose transporter), member 1 polymorphisms on 2-[fluorine-18]-fluoro-2-deoxy-Dglucose-uptake with a combination of polymorphisms of hypoxia-inducible factor 1 alpha, apurinic/apyimidinic endonuclease, and vascular endothelial growth factor A in a hypoxia-related pathway
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