These genotype frequencies were very similar to frequencies reported in a previous study by Kuwai et al. [28]. Kuwai and colleagues reported a CT polymorphism in 11%, but an absence of TT in the Japanese population. Moreover, despite the association of HIF1A polymorphisms with HIF-1a expression, there was no association
of polymorphisms with the expression of the down-stream proteins encoded by SLC2A1 and VEGFA [8]. VEGFA is the major mediator of angiogenesis and vascular permeability. PI3K Inhibitor Library cell assay Transcription of VEGFA under hypoxic conditions depends on HIF-1a induction. Although FDG-uptake has been correlated significantly with VEGFA expression in patients with NSCLC [18], we did not observe an effect of the VEGFA+936C>T polymorphism on FDG-uptake. An association between the VEGFA+936C>T polymorphism and FDG-uptake has been rarely reported for patients with NSCLC. Wolf et al. [11] reported that the VEGFA+936C>T polymorphism is associated with FDG-uptake in breast cancer patients. The FDG-uptake data in the study by Wolf et al. [11] was expressed as categorical data (low, medium, and high uptake) and not as a SUVmax, as in the
present study; thus, we cannot directly compare the values of SUVmax obtained in the present study. Another possible explanation was a difference in the study population. The population in the study by Wolf et al. [11] was breast cancer patients, while the study population in the present study was lung cancer patients. Recently, several functional SNPs of VEFGA have been identified HDAC inhibitor that are associated with survival in patients with early stage NSCLC [29, 30]. Well-documented functional SNPs, such as VEGFA +405G>C and -460T>C, should be evaluated to identify the association between VEGFA gene polymorphisms and FDG-uptake. There were several limitations to this study. We did not evaluate the association
between hypoxia-related gene polymorphisms and FDG-uptake in patients with early stage NSCLC. Although the SLC2A1 -2841A>T polymorphism in combination with the APEX1 Asp148Glu polymorphism was associated with FDG uptake in this study, this result was based on a statistical comparison rather than a functional study. Adenosine Another limitation was the potential effect of unknown SNPs of hypoxia-related genes on FDG-uptake, as we only analyzed documented-functional SNPs. Thus, additional investigations of polymorphisms in entire hypoxia-induced pathway on FDG-uptake are needed. In summary, the SLC2A1 -2841A>T polymorphism was associated with FDG-uptake in combination with the APEX1 TT genotype in patients with squamous cell carcinoma. Our findings suggest that a newly developed tracer for PET could be affected by genetic polymorphisms. However, further studies are required to validate these results.