The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer
Abstract
:1. Introduction
2. Results and Discussion
2.1. Patient Characteristics
Test cohort | Validation cohort | |
---|---|---|
Number (%) | Number (%) | |
Sum of the percentages do not always equal 100 % due to rounding of data. Not all patients had complete patient characteristics available. | ||
Sex | ||
Male | 98 (51) | 159 (54) |
Female | 93 (49) | 136 (46) |
Age (years) | ||
Mean (SD) | 70.1 (11.6) | 70.5 (11.2) |
Range | 31–97 | 33–92 |
pT category | ||
1–3 | 159 (83) | 248 (84) |
4 | 32 (17) | 47 (16) |
pN category | ||
0 | 99 (52) | 163 (55) |
1–2 | 92 (48) | 132 (45) |
Stage | ||
II | 98 (51) | 163 (55) |
III | 93 (49) | 132 (45) |
Localization | ||
Colon | 121 (63) | 197 (67) |
Rectum | 70 (37) | 98 (33) |
Vascular invasion | ||
Yes | 11 (9) | 35 (12) |
No | 111 (91) | 249 (88) |
Neuronal invasion | ||
Yes | 11 (9) | 31 (12) |
No | 109 (91) | 236 (88) |
Peritoneal perforation | ||
Yes | 26 (14) | 38 (13) |
No | 160 (86) | 253 (87) |
Adjuvant chemotherapy | ||
No | 157 (82) | 232 (81) |
Yes | 34 (18) | 53 (19) |
5-FU/Leucovorin or capecitabine | 34 (100) | 28 (53) |
XELOX | 0 (0) | 25 (47) |
−2578 C/A SNP | ||
CC | 47 (25) | 80 (27) |
CA | 85 (45) | 147 (50) |
AA | 59 (31) | 68 (23) |
−460 C/T SNP | ||
CC | 59 (31) | 69 (23) |
CT | 85 (45) | 146 (49) |
TT | 47 (25) | 80 (27) |
405 G/C SNP | ||
GG | 95 (50) | 128 (43) |
GC | 74 (39) | 129 (44) |
CC | 22 (12) | 38 (13) |
2.2. The Prognostic Value of VEGF-A SNPs
Disease free survival (DFS) | |||||||||
Test cohort | Validation cohort | ||||||||
VEGF-A SNP and genotype comparison* | Events | HR (95% CI) | p-value | VEGF-A SNP and genotype comparison* | Events | HR (95% CI) | p-value | ||
−2578 C/A | −2578 C/A | ||||||||
CC (NR) v CA (3.3) | 19 v 55 | 0.47 (0.30–0.75) | <0.01 | CC (5.6) v CA (5.8) | 17 v 49 | 0.62 (0.37–1.03) | 0.09 | ||
CC (NR) v AA (8.5) | 19 v 29 | 0.83 (0.47–1.46) | 0.52 | CC (5.6) v AA (NR) | 17 v 15 | 1.13 (0.57–2.26) | 0.73 | ||
CA (3.3) v AA (8.5) | 55 v 29 | 1.78 (1.16–2.74) | 0.01 | CA (5.8) v AA (NR) | 49 v 15 | 1.75 (1.05–2.93) | >0.05 | ||
CA v CC + AA | 1.93 (1.29–2.89) | <0.01 | CA v CC + AA | 1.68 (1.09–2.60) | 0.02 | ||||
−460 C/T | −460 C/T | ||||||||
CC (8.5) v CT (3.3) | 29 v 55 | 0.56 (0.37–0.86) | 0.01 | CC (NR) v CT (5.8) | 15 v 50 | 0.55 (0.33–0.91) | 0.04 | ||
CC (8.5) v TT (NR) | 29 v 19 | 1.21 (0.68–2.14) | 0.52 | CC (NR) v TT (5.6) | 15 v 16 | 0.91 (0.45–1.85) | 0.80 | ||
CT (3.3) v TT (NR) | 55 v 19 | 2.11 (1.33–3.35) | <0.01 | CT (5.8) v TT (5.6) | 50 v 16 | 1.73 (1.05–2.87) | >0.05 | ||
CT v CC + TT | 1.93 (1.29–2.89) | <0.01 | CT v CC + TT | 1.78 (1.15–2.75) | 0.01 | ||||
405 G/C | 405 G/C | ||||||||
GG (7.5) v GC (4.3) | 50 v 43 | 0.73 (0.48–1.11) | 0.13 | GG (NR) v GC (5.0) | 24 v 48 | 0.41 (0.26–0.65) | <0.01 | ||
GG (7.5) v CC (NR) | 50 v 10 | 1.16 (0.61–2.22) | 0.67 | GG (NR) v CC (NR) | 24 v 9 | 0.69 (0.30–1.60) | 0.34 | ||
GC (4.3) v CC (NR) | 43 v 10 | 1.55 (0.84–2.85) | 0.21 | GC (5.0) v CC (NR) | 48 v 9 | 1.66 (0.90–3.06) | 0.16 | ||
GC v GG + CC | 1.40 (0.93–2.12) | 0.09 | GC v GG + CC | 2.22 (1.42–3.46) | <0.01 | ||||
Overall survival (OS) | |||||||||
Test cohort | Validation cohort | ||||||||
VEGF-A SNP and genotype comparison* | Events | HR (95% CI) | p-value | VEGF-A SNP and genotype comparison* | Events | HR (95% CI) | p-value | ||
−2578 C/A | −2578 C/A | ||||||||
CC (NR) v CA (4.7) | 18 v 55 | 0.46 (0.29–0.74) | <0.01 | CC (6.1) v CA (NR) | 12 v 40 | 0.55 (0.31–0.97) | 0.06 | ||
CC (NR) v AA (8.8) | 18 v 29 | 0.79 (0.44–1.40) | 0.42 | CC (6.1) v AA (7.0) | 12 v 15 | 0.84 (0.39–1.79) | 0.65 | ||
CA (4.7) v AA (8.8) | 55 v 29 | 1.71 (1.12–2.63) | 0.02 | CA (NR) v AA (7.0) | 40 v 15 | 1.38 (0.79–2.41) | 0.28 | ||
CA v CC + AA | 1.89 (1.27–2.82) | <0.01 | CA v CC v AA | 1.57 (0.97–2.54) | 0.07 | ||||
−460 C/T | −460 C/T | ||||||||
CC (8.8) v CT (4.7) | 29 v 55 | 0.58 (0.38–0.90) | 0.02 | CC (7.0) v CT (NR) | 15 v 41 | 0.69 (0.40–1.20) | 0.22 | ||
CC (8.8) v TT (NR) | 29 v 18 | 1.27 (0.72–2.26) | 0.42 | CC (7.0) v TT (NR) | 15 v 11 | 1.26 (0.58–2.72) | 0.56 | ||
CT (4.7) v TT (NR) | 55 v 18 | 2.15 (1.35–3.43) | <0.01 | CT (NR) v TT (NR) | 41 v 11 | 1.99 (1.13–3.53) | 0.04 | ||
CT v CC + TT | 1.89 (1.27–2.82) | <0.01 | CT v CC + TT | 1.66 (1.03–2.68) | 0.04 | ||||
405 G/C | 405 G/C | ||||||||
GG (8.3) v GC (4.8) | 50 v 43 | 0.72 (0.47–1.10) | 0.11 | GG (NR) v GC (5.8) | 23 v 39 | 0.51 (0.31–0.84) | 0.01 | ||
GG (8.3) v CC (NR) | 50 v 9 | 1.33 (0.70–2.54) | 0.43 | GG (NR) v CC (NR) | 23 v 5 | 1.21 (0.49–3.02) | 0.70 | ||
GC (4.8) v CC (NR) | 43 v 9 | 1.82 (0.99–3.35) | 0.10 | GC (5.8) v CC (NR) | 39 v 5 | 2.25 (1.11–4.58) | 0.08 | ||
GC v GG + CC | 1.46 (0.97–2.20) | 0.06 | GC v GG + CC | 2.00 (1.23–3.25) | <0.01 |
Genotypes | Disease free survival (DFS) | Overall survival (OS) | ||
---|---|---|---|---|
HR (95% CI) | p-value | HR (95% CI) | p-value | |
−2578 C/A | ||||
CC | 1 | 1 | ||
CA | 1.98 (1.10–3.56) | 0.02 | 1.92 (0.98–3.76) | 0.06 |
AA | 1.10 (0.53–2.28) | 0.80 | 1.32 (0.60–2.92) | 0.49 |
−460 C/T | ||||
CC | 1 | 1 | ||
CT | 1.81 (0.99–3.31) | 0.06 | 1.46 (0.79–2.72) | 0.23 |
TT | 0.89 (0.42–1.87) | 0.76 | 0.73 (0.32–1.64) | 0.44 |
405 G/C | ||||
GG | 1 | 1 | ||
GC | 1.79 (1.06–3.01) | 0.03 | 1.52 (0.88–2.63) | 0.13 |
CC | 0.98 (0.43–2.26) | 0.97 | 0.73 (0.27–1.98) | 0.53 |
2.3. Haplotype Analysis
Disease free survival (DFS) | ||||||
Test cohort | Validation cohort | |||||
HR (95% CI) | p-value | HR (95% CI) | p-value | |||
Remaining combinations | 1 | Remaining combinations | 1 | |||
(CTG, ACG) | 1.85 (0.95–3.62) | 0.07 | (CTG, ACG) | 0.98 (0.44–2.18) | 0.97 | |
(CTC, ACG) | 2.04 (1.14–3.67) | 0.02 | (CTC, ACG) | 2.46 (1.49–4.06) | <0.01 | |
Overall survival (OS) | ||||||
Test cohort | Validation cohort | |||||
HR (95% CI) | p-value | HR (95% CI) | p-value | |||
Remaining combinations | 1 | Remaining combinations | 1 | |||
(CTG, ACG) | 1.72 (0.89–3.36) | 0.11 | (CTG, ACG) | 0.95 (0.40–2.21) | 0.90 | |
(CTC, ACG) | 2.15 (1.21–3.82) | 0.01 | (CTC, ACG) | 2.07 (1.20–3.57) | 0.01 |
2.4. Discussion
3. Experimental Section
3.1. Study Population
3.2. Analysis of Single Nucleotide Polymorphism
3.3. Statistical Analysis
4. Conclusions
Acknowledgements
References
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Hansen, T.F.; Spindler, K.-L.G.; Andersen, R.F.; Lindebjerg, J.; Kølvraa, S.; Brandslund, I.; Jakobsen, A. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer. Cancers 2010, 2, 1405-1418. https://doi.org/10.3390/cancers2031405
Hansen TF, Spindler K-LG, Andersen RF, Lindebjerg J, Kølvraa S, Brandslund I, Jakobsen A. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer. Cancers. 2010; 2(3):1405-1418. https://doi.org/10.3390/cancers2031405
Chicago/Turabian StyleHansen, Torben F., Karen-Lise G. Spindler, Rikke F. Andersen, Jan Lindebjerg, Steen Kølvraa, Ivan Brandslund, and Anders Jakobsen. 2010. "The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer" Cancers 2, no. 3: 1405-1418. https://doi.org/10.3390/cancers2031405