Introduction
Materials and methods
1. Patient characteristics
Single nucleotide polymorphism Selection
Genotyping
Gene | SNP name (rs number) | Primer sequence | Tm | |
---|---|---|---|---|
VEGFA
| +936C>T (rs3025039) | Forward | CACTTTGGGTCCGGAGGG | |
Reverse | TGATTTAGCAGCAAGAAAAATAAA | 55 | ||
Genotyping | GGCGAATCCAATTCCAAGAGGGACC | |||
HIF1A
| P582S (rs11549465) | Forward | TATATCCCAATGGATGATGACTT | |
Reverse | TTCTTGTATTTGAGTCTGCTGG | 55 | ||
Genotyping | GTTACGTTCCTTCGATCAGTTGTCA | |||
HIF1A
| A588T (rs11549467) | Forward | AGATTTAGACTTGGAGATGTTAGCTC | |
Reverse | AATACTGTAACTGTGCTTTGAGGAC | 55 | ||
Genotyping | GTTGTCAYCATTAGAAAGCAGTTCC | |||
SLC2A1
| -2841A>T (rs710218) | Forward | CCTTTGCACATGCTCTTC | |
Reverse | GCCACCTTGTCCTTCTCT | 60 | ||
Genotyping | CCTGTGGTACAAGTTCTGC | |||
APEX1
| D148E (rs1130409) | Forward | CAGTGCCCACTCAAAGTT | |
Reverse | CTTGCGAAAGGCTTCAT | 60 | ||
Genotyping | GGCCTTCCTGATCATGCTCCTC |
F-18 FDG PET
Visual assessment and quantitative analysis
Statistical analysis
Results
1. Patient characteristics
Adenocarcinoma | Squamous cell carcinoma | ||
---|---|---|---|
Age | |||
Male | 64.2 ± 8.5 (n = 41) | 66.0 ± 8.1 (n = 73) | |
Female | 59.2 ± 10.8 (n = 34) | 67.7 ± 10.0 (n = 6) | |
Smoking habit | |||
Never | 35 (46.7%) | 7 (8.9%) | |
Smoker | 40 (53.3%) | 72 (91.1%) | |
Stage | |||
Stage I + II | 14 (18.7%) | 12 (15.2%) | |
Stage III + IV | 61 (81.3%) | 67 (84.8%) | |
T stage | |||
1 | 12 (16.0%) | 4 (5.1%) | |
2 | 2 (2.7%) | 8 (10.1%) | |
3 | 19 (25.3%) | 43 (54.4%) | |
4 | 42 (56.0%) | 24 (30.4%) |
2. Genotype information
Target gene polymorphism (rs number) | Genotype | No. patients | (%) | Allele frequencies | Hardy-Weinberg equilibrium | |
---|---|---|---|---|---|---|
SLC2A1
-2841A>T
| AA | 78 | (51.7%) | A:T | 0.705:0.295 | 0.2579 |
(rs710218)
| AT | 57 | (37.7%) | |||
TT | 16 | (10.6%) | ||||
VEGFA
+936C>T
| CC | 102 | (67.1%) | C:T | 0.819:0.181 | 0.2579 |
(rs3025039)
| CT | 45 | (29.6%) | |||
TT | 5 | (3.3%) | ||||
APEX1
Asp148Glu
| TT | 55 | (36.4%) | T:G | 0.589:0.411 | 0.3929 |
(rs1130409)
| TG | 68 | (45.0%) | |||
GG | 28 | (18.5%) | ||||
HIF1A
Pro582Ser
| CC | 139 | (90.8%) | C:T | 0.954:0.046 | 0.5541 |
(rs11549465)
| CT | 14 | (9.2%) | |||
TT | 0 | (0.0%) | ||||
HIF1A
Ala588Thr
| GG | 137 | (90.1%) | G:A | 0.951:0.049 | 0.5219 |
(rs11549467)
| GA | 15 | (9.9%) | |||
AA | 0 | (0.0%) |
3. Association of SNPs with the mean SUVmax
Genes | Genotype | SUVmax | P* | Domonant model | SUVmax |
P
†
| Recessive mode | SUVmax |
P
†
|
---|---|---|---|---|---|---|---|---|---|
SLC2A1
-2841A>T
| AA (n = 41) | 9.40 ± 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 |
4. Association of SNPs on the mean SUVmax in squamous cell carcinomas
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) |