Table 2.
Response, PFS, and OS by polymorphisms and HER2 amplification status
| Response |
Progression-free survival |
Overall survival |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Polymorphisms | n | Yes | No | Pa | Median (95% CI) | HR (95% CI)c | Pa | Median (95% CI) | HR (95% CI)c | Pa |
| CCND1 A870G | 0.71 | 0.32 | 0.73 | |||||||
| A/A | 16 | 2 (13%) | 14 (88%) | 3.0 (2.0–4.2) | 1 (Ref) | 6.3 (3.3–11.6) | 1 (Ref) | |||
| A/Gb | 32 | 8 (20%) | 32 (80%) | 3.0 (2.6–4.3) | 0.74 (0.40–1.37) | 5.8 (3.5–9.1) | 1.12 (0.58–2.19) | |||
| G/Gb | 8 | |||||||||
| COX2 G765C | 0.34 | 0.26 | 0.30 | |||||||
| G/G | 47 | 7 (15%) | 40 (85%) | 3.0 (2.5–3.8) | 1 (Ref) | 5.4 (3.8–8.1) | 1 (Ref) | |||
| G/Cb | 2 | 3 (33%) | 6 (67%) | 5.7 (2.6–5.8+) | 0.63 (0.26–1.48) | 9.1 (3.5–23.1) | 0.62 (0.24–1.57) | |||
| C/Cb | 7 | |||||||||
| EGF A61G | 0.73 | 0.92 | 0.85 | |||||||
| G/G | 19 | 3 (16%) | 16 (84%) | 3.1 (2.9–4.3) | 1 (Ref) | 5.8 (3.7–14.7) | 1 (Ref) | |||
| G/A | 27 | 6 (22%) | 21 (78%) | 2.9 (2.0–4.3) | 1.10 (0.59–2.05) | 5.6 (3.3–8.6) | 1.20 (0.62–2.33) | |||
| A/A | 10 | 1 (10%) | 9 (90%) | 2.6 (1.6–8.6) | 1.16 (0.51–2.63) | 8.1 (1.1–15.9) | 1.06 (0.45–2.52) | |||
| EGFR G497A | 0.16 | 0.33 | 0.087 | |||||||
| G/G | 24 | 2 (8%) | 22 (92%) | 2.9 (2.5–4.3) | 1 (Ref) | 4.2 (2.6–8.6) | 1 (Ref) | |||
| G/Ab | 24 | 8 (25%) | 24 (75%) | 3.3 (1.8–4.3) | 0.76 (0.43–1.36) | 7.3 (4.2–14.8) | 0.61 (0.33–1.10) | |||
| A/Ab | 8 | |||||||||
| HER2 G655A | 0.48 | 0.82 | 0.45 | |||||||
| A/A | 35 | 5 (14%) | 30 (86%) | 2.9 (1.8–4.2) | 1 (Ref) | 4.4 (3.5–8.1) | 1 (Ref) | |||
| A/G | 21 | 5 (24%) | 16 (76%) | 3.8 (2.8–4.4) | 0.94 (0.53–1.66) | 8.6 (3.8–14.7) | 0.80 (0.43–1.46) | |||
| IL8 T251A | 0.36 | 0.23 | 0.23 | |||||||
| T/T | 19 | 3 (16%) | 16 (84%) | 3.1 (1.7–4.1) | 1 (Ref) | 5.4 (3.5–7.3) | 1 (Ref) | |||
| T/A | 24 | 3 (13%) | 21 (88%) | 2.9 (2.5–4.3) | 0.86 (0.45–1.65) | 6.3 (3.1–15.4) | 0.61 (0.32–1.19) | |||
| A/A | 13 | 4 (31%) | 9 (69%) | 4.2 (3.0–5.8) | 0.54 (0.25–1.20) | 5.8 (2.0–22.9) | 0.58 (0.25–1.36) | |||
| MTHFR C677T | 0.72 | 0.96 | 0.99 | |||||||
| C/C | 22 | 3 (14%) | 19 (86%) | 3.0 (1.7–4.4) | 1 (Ref) | 8.1 (3.5–11.6) | 1 (Ref) | |||
| C/Tb | 26 | 7 (21%) | 27 (79%) | 3.0 (2.6–4.2) | 1.01 (0.57–1.80) | 5.0 (3.8–7.3) | 1.01 (0.55–1.82) | |||
| T/Tb | 8 | |||||||||
| MTHFR A1298C | 0.16 | 0.071 | 0.23 | |||||||
| A/A | 31 | 8 (26%) | 23 (74%) | 3.0 (2.6–5.3) | 1 (Ref) | 7.2 (4.2–9.3) | 1 (Ref) | |||
| A/Cb | 20 | 2 (8%) | 23 (92%) | 3.0 (1.7–4.1) | 1.63 (0.92–2.91) | 4.4 (3.0–8.6) | 1.42 (0.79–2.56) | |||
| C/Cb | 5 | |||||||||
| TS-5′UTR | 1.00 | 0.87 | 0.26 | |||||||
| 2R/2R, 2R/3C, 3C/3C | 20 | 3 (15%) | 17 (85%) | 3.1 (2.6–4.4) | 1 (Ref) | 5.4 (3.1–12.9) | 1 (Ref) | |||
| 2R/3G, 3G/3C | 26 | 5 (19%) | 21 (81%) | 2.9 (1.8–4.2) | 1.07 (0.57–2.01) | 8.1 (3.8–14.8) | 0.67 (0.34–1.33) | |||
| 3G/G | 10 | 2 (20%) | 8 (80%) | 2.8 (1.6–4.3) | 1.22 (0.56–2.67) | 4.2 (2.2–8.6) | 1.17 (0.51–2.69) | |||
| TS-3′UTR | 0.75 | 0.97 | 0.68 | |||||||
| +/+ | 14 | 3 (21%) | 11 (79%) | 3.1 (1.7–4.3) | 1 (Ref) | 5.4 (3.5–11.4) | 1 (Ref) | |||
| +/− | 22 | 3 (14%) | 19 (86%) | 2.6 (1.8–5.3) | 0.96 (0.45–2.05) | 5.8 (2.9–14.7) | 0.73 (0.32–1.64) | |||
| −/− | 20 | 4 (20%) | 16 (80%) | 3.0 (1.8–4.3) | 1.03 (0.49–2.18) | 6.1 (3.8–8.6) | 0.88 (0.40–1.95) | |||
| VEGF C936T | 1.00 | 0.78 | 0.66 | |||||||
| C/C | 42 | 8 (19%) | 34 (81%) | 3.0 (2.8–4.3) | 1 (Ref) | 5.8 (3.8–9.1) | 1 (Ref) | |||
| C/Tb | 12 | 2 (14%) | 12 (86%) | 2.6 (1.7–4.3) | 0.91 (0.48–1.75) | 5.6 (2.6–8.1) | 1.16 (0.59–2.30) | |||
| T/Tb | 2 | |||||||||
| HER2 status | 0.66 | 0.95 | 0.80 | |||||||
| Amplified | 8 | 1 (13%) | 7 (88%) | 4.3 (1.6–8.5) | 1 (Ref) | 6.3 (2.6–16.7) | 1 (Ref) | |||
| Not amplified | 34 | 8 (24%) | 26 (76%) | 3.0 (2.8–4.3) | 1.02 (0.46–2.28) | 5.8 (3.8–8.6) | 1.10 (0.49–2.47) | |||
a
Based on Fisher exact test for response and log-rank test for PFS and OS.
b
Dominant model: combining patients carrying heterozygous and homozygous variant genotypes together for outcome analyses.
c
Based on the method described by Berry and colleagues (38).