40 ± 2.63 0.155 AA 9.40 ± 2.63 0.565 AA + AT 9.07 ± 2.79 0.130   AT (n = 29) 8.60 ± 2.98   AT + TT 9.04 ± 2.94   TT 10.64 ± 2.26     TT (n = 8) 10.64 ± 2.26               VEGFA +936C>T CC (n = 54) 9.29 ± 2.66 0.816 CC 9.29 ± 2.66 0.774 CC + CT 9.20 ± 2.80 0.663   CT (n = 20) 8.95 ± 3.23   CT + TT 9.10 ± 3.06   TT 9.83 ± 2.25     TT (n = 4) 9.83 ± 2.25               APEX1 Asp148Glu TT (n = 28) 8.89 ± 3.04 0.522 TT 8.89 ± 3.04 0.412 TT + TG 9.30 ± 2.90 0.672   TG (n = 34) 9.64 ± 2.79   TG + GG 9.43 ± 2.62   GG

8.97 ± 2.23     GG (n = 16) 8.97 ± 2.23               HIF1A Pro582Ser CC (n = 69) 9.32 ± 2.84 0.671               CT (n = 10) 8.92 ± 2.35               HIF1A Ala588Thr GG (n = 68) 9.18 ± 2.74 0.664               GA (n = 10) 9.59 ± 3.11               *ANOVA † t-test 4. Association of SNPs on the mean GF120918 in vitro SUVmax in squamous VEGFR inhibitor cell carcinomas We analyzed subgroups according to the combinations of SLC2A1, VEGFA, APEX1, and HIF1A polymorphisms in patients with squamous cell carcinomas. The SLC2A1 -2841A>T polymorphism was significantly associated with the mean SUVmax in the recessive model of SLC2A1 -2841A>T in combination with the APEX1 polymorphism (Table 5). For the TT genotype of APEX1, the SLC2A1 TT genotype had a higher SUVmax than the AA + AT genotype (12.47 ± 1.33 versus 8.46 ± 2.90, respectively; P = 0.028, Table 5). The other combinations

buy GSK2245840 of SLC2A1, VEGFA, and HIF1A polymorphisms were (-)-p-Bromotetramisole Oxalate not associated with the mean SUVmax. Table 5 Association between the SLC2A1 -2841A>T gene polymorphism and the mean SUVmax in patients with squamous cell carcinoma according to the APEX1 genotype APEX1 genotype Gene genotype SUVmax P* Dominant model SUVmax P † Recessive mode SUVmax P † TT SLC2A1 -2841A>T AA (n = 13) 8.68 ± 2.40 0.086 AA 8.68 ± 2.40 0.742 AA + AT 8.46 ± 2.90 0.028     AT (n = 12) 8.22

± 3.47   AT + TT 9.07 ± 3.58   TT 12.47 ± 1.33       TT (n = 3) 12.47 ± 1.33               TG SLC2A1 -2841A>T AA (n = 20) 9.72 ± 3.00 0.984 AA 9.72 ± 3.00 0.857 AA + AT 9.66 ± 2.93 0.932     AT (n = 9) 9.53 ± 2.94   AT + TT 9.54 ± 2.56   TT 9.54 ± 2.00       TT (n = 5) 9.54 ± 2.01               GG SLC2A1 -2841A>T AA (n = 8) 9.81 ± 1.97   AA 9.81 ± 1.97 0.134 AA + AT 8.97 ± 2.23       AT (n = 8) 8.13 ± 2.26   AT + TT 8.13 ± 2.26   TT         TT (n = 0)                 *ANOVA † t-test Discussion Although there have been several reports that have described an association between hypoxia-related genes and SUVmax in patients with lung cancer [17, 18], this is the first study that has evaluated the impact of SLC2A1 gene polymorphisms on FDG-uptake in conjunction with the HIF-1a-activated transcription pathway in patients with NSCLC. With this pathway-based approach, we have demonstrated that SLC2A1 TT is statistically associated with a high FDG-uptake in combination with the TT genotype of APEX1 in patients with the squamous cell type of NSCLC.