These results suggested the involvement of APEX1 in the development of lung cancer. Recently, APEX polymorphisms have been the focus of studies involving several different types of cancer, including colorectal, breast, and non-small cell lung cancer (NSCLC). One important mammalian redox modulator is the bifunctional enzyme Redox factor-1 (Ref-1, also termed APEX1), that promotes transcriptional activation of HIF-1 or hypoxia inducible factor-like factor (HLF) by reducing C-terminal domain of HIF-1 or HLF, although the major role of this enzyme is DNA base excision repair. These findings suggest a potential role of the VEGFA 936C>T polymorphism for the variability of FDG uptake in tumor tissues. The T variant, which is linked to lower VEGFA levels, has been associated with colon cancer and low FDG uptake. A C>T polymorphism at position 936 in the 3' untranslated region of the VEGFA gene has been associated with the plasma levels of VEGFA. VEGFA is the major mediator of angiogenesis and vascular permeability and transcription of this gene under hypoxic conditions depends on HIF-1a induction. The expression of the downstream SLC2A1 and vascular endothelial growth factor ( VEGF) genes are regulated by a HIF1A-activated transcription pathway. showed that a HIF1A gene polymorphism affected HIF-1a protein expression. Indeed, 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.
HIF-1a overexpression and enhanced transcriptional activity are linked to tumor initiation and progression. Many cellular proteins interact with or are under the control of HIF1-a. HIF-1a regulates SLC2A1 gene expression in cells that are subjected to hypoxic conditions. Hypoxia-inducible factor 1a (HIF-1a) controls oxygen delivery via angiogenesis and metabolic adaptation to hypoxia via glycolysis. The SLC2A1 (also called glucose transporter type 1, GLUT1) gene is the primary glucose transporter gene in human lung cancer. Moreover, FDG-PET is used for treatment planning and is used to evaluate the response to therapy. FDG-PET has been shown to have the ability to diagnose disease. Positron emission tomography (PET) imaging of malignant tumors with 2-fluoro-2-deoxy-D-glucose (FDG) as a tracer (FDG uptake depends on glucose uptake) is a non-invasive diagnostic, and prognostic tool that measures tumor metabolism. Our findings suggest that a newly developed tracer for positron emission tomography could be affected by genetic polymorphisms. ConclusionĪ 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. 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.
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 solute carrier family 2 (facilitated glucose transporter), member 1 -2841A>T polymorphism was significantly associated with 2-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. We 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-fluoro-2-deoxy-D-glucose-uptake among 154 patients with non-small-cell lung cancer. We have analyzed the effect of solute carrier family 2 (facilitated glucose transporter), member 1 polymorphisms on 2-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. Positron emission tomography imaging of lung cancers with 2-fluoro-2-deoxy-D-glucose is a non-invasive diagnostic, and prognostic tool that measures tumor metabolism.
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