Table 1.
Association Between Gene Polymorphism and Clinical Outcome
| N | Disease Control | Progression-Free Survival | Overall Survival | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PR + SD | PD | P value* | Median (95% CI), mo | Univariate HR (95% CI)† | P value* | Multivariable HR (95% CI)‡ | P value* | Median (95% CI), mo | Univariate HR (95% CI)† | P value* | Multivariable HR (95% CI)‡ | P value* | ||
| CCL5 rs2280789 | .42 | .56 | .21 | .36 | .039 | |||||||||
| A/A | 27 | 13 (59%) | 9 (41%) | 2.3 (1.8, 3.3) | 1 (Reference) | 1 (Reference) | 7.9 (4.0, 29.9) | 1 (Reference) | 1 (Reference) | |||||
| A/G | 35 | 12 (46%) | 14 (54%) | 2.0 (1.5, 2.5) | 1.01 (0.61, 1.69) | 1.20 (0.72, 2.02) | 8.1 (4.6, 12.6) | 1.19 (0.64, 2.22) | 1.53 (0.81, 2.91) | |||||
| G/G | 17 | 6 (38%) | 10 (63%) | 2.0 (1.7, 4.7) | 0.76 (0.41, 1.43) | 0.68 (0.36, 1.30) | 12.9 (5.0, 27.7) | 0.71 (0.32, 1.57) | 0.56 (0.25, 1.27) | |||||
| .39 | .28 | .11 | .19 | .032 | ||||||||||
| Any A | 62 | 25 (52%) | 23 (48%) | 2.0 (1.8, 2.7) | 1 (Reference) | 1 (Reference) | 7.9 (5.8, 11.8) | 1 (Reference) | 1 (Reference) | |||||
| G/G | 17 | 6 (38%) | 10 (63%) | 2.0 (1.7, 4.7) | 0.76 (0.43, 1.32) | 0.62 (0.35, 1.11) | 12.9 (5.0, 27.7) | 0.64 (0.32, 1.28) | 0.45 (0.21, 0.93) | |||||
| CCL5 rs3817655 | .74 | .60 | .40 | .52 | .12 | |||||||||
| A/A | 27 | 12 (55%) | 10 (45%) | 2.0 (1.8, 3.2) | 1 (Reference) | 1 (Reference) | 7.1 (4.0, 29.9) | 1 (Reference) | 1 (Reference) | |||||
| A/T | 34 | 12 (48%) | 13 (52%) | 2.0 (1.6, 3.7) | 0.87 (0.52, 1.46) | 0.98 (0.58, 1.67) | 8.7 (4.6, 12.6) | 1.00 (0.54, 1.86) | 1.28 (0.67, 2.44) | |||||
| T/T | 18 | 7 (41%) | 10 (59%) | 1.9 (1.7, 4.5) | 0.75 (0.40, 1.38) | 0.67 (0.35, 1.26) | 12.9 (5.0, 27.7) | 0.68 (0.32, 1.47) | 0.57 (0.26, 1.24) | |||||
| .58 | .40 | .18 | .25 | .055 | ||||||||||
| Any A | 61 | 24 (51%) | 23 (49%) | 2.0 (1.8, 2.7) | 1 (Reference) | 1 (Reference) | 7.9 (5.8, 11.8) | 1 (Reference) | 1 (Reference) | |||||
| T/T | 18 | 7 (41%) | 10 (59%) | 1.9 (1.7, 4.5) | 0.81 (0.47, 1.39) | 0.67 (0.38, 1.19) | 12.9 (5.0, 27.7) | 0.68 (0.35, 1.34) | 0.50 (0.25, 1.02) | |||||
| CCR5 rs1799988 | .019 | .25 | .50 | .43 | .55 | |||||||||
| T/T | 25 | 5 (25%) | 15 (75%) | 1.8 (1.1, 2.3) | 1 (Reference) | 1 (Reference) | 6.3 (4.0, 27.2) | 1 (Reference) | 1 (Reference) | |||||
| T/C | 29 | 12 (50%) | 12 (50%) | 2.3 (1.8, 3.3) | 0.65 (0.37, 1.14) | 0.71 (0.40, 1.26) | 9.6 (5.0, 13.6) | 0.88 (0.45, 1.70) | 0.88 (0.45, 1.73) | |||||
| C/C | 24 | 14 (70%) | 6 (30%) | 2.7 (1.6, 4.5) | 0.74 (0.42, 1.30) | 0.80 (0.45, 1.42) | 12.6 (6.5, 15.5) | 0.64 (0.32, 1.30) | 0.68 (0.33, 1.39) | |||||
| .016 | .11 | .26 | .35 | .43 | ||||||||||
| T/T | 25 | 5 (25%) | 15 (75%) | 1.8 (1.1, 2.3) | 1 (Reference) | 1 (Reference) | 6.3 (4.0, 27.2) | 1 (Reference) | 1 (Reference) | |||||
| Any C | 53 | 26 (59%) | 18 (41%) | 2.5 (1.8, 3.3) | 0.69 (0.42, 1.12) | 0.75 (0.46, 1.23) | 10.3 (6.7, 12.9) | 0.76 (0.42, 1.38) | 0.78 (0.42, 1.44) | |||||
| .031 | .81 | .86 | .22 | .30 | ||||||||||
| Any T | 54 | 17 (39%) | 27 (61%) | 2.0 (1.8, 2.3) | 1 (Reference) | 1 (Reference) | 7.8 (5.0, 10.8) | 1 (Reference) | 1 (Reference) | |||||
| C/C | 24 | 14 (70%) | 6 (30%) | 2.7 (1.6, 4.5) | 0.94 (0.58, 1.54) | 0.96 (0.58, 1.58) | 12.6 (6.5, 15.5) | 0.69 (0.38, 1.26) | 0.73 (0.40, 1.33) | |||||
| CCL3 rs1130371 | .31 | .064 | .41 | .76 | .23 | |||||||||
| G/G | 36 | 16 (57%) | 12 (43%) | 2.5 (1.7, 4.1) | 1 (Reference) | 1 (Reference) | 8.1 (4.6, 12.9) | 1 (Reference) | 1 (Reference) | |||||
| Any A | 42 | 15 (42%) | 21 (58%) | 2.0 (1.8, 2.4) | 1.48 (0.91, 2.39) | 1.23 (0.75, 2.01) | 9.6 (6.1, 12.9) | 1.09 (0.62, 1.90) | 0.70 (0.39, 1.26) | |||||
| CCL4 rs1634517 | .12 | .12 | .14 | .13 | .17 | |||||||||
| C/C | 42 | 20 (57%) | 15 (43%) | 2.5 (1.7, 3.7) | 1 (Reference) | 1 (Reference) | 8.1 (5.1, 13.6) | 1 (Reference) | 1 (Reference) | |||||
| C/A | 26 | 6 (30%) | 14 (70%) | 1.9 (1.6, 2.4) | 1.60 (0.95, 2.69) | 1.67 (1.00, 2.78) | 11.8 (7.1, 15.3) | 0.89 (0.48, 1.68) | 0.79 (0.41, 1.50) | |||||
| A/A | 9 | 5 (63%) | 3 (38%) | 2.0 (0.6, 4.5) | 1.40 (0.66, 2.97) | 1.35 (0.64, 2.85) | 6.1 (1.5, 13.9) | 1.96 (0.91, 4.20) | 1.76 (0.80, 3.86) | |||||
| .21 | .043 | .058 | .71 | .96 | ||||||||||
| C/C | 42 | 20 (57%) | 15 (43%) | 2.5 (1.7, 3.7) | 1 (Reference) | 1 (Reference) | 8.1 (5.1, 13.6) | 1 (Reference) | 1 (Reference) | |||||
| Any A | 35 | 11 (39%) | 17 (61%) | 2.0 (1.8, 2.4) | 1.54 (0.96, 2.50) | 1.58 (0.98, 2.53) | 9.6 (6.1, 12.9) | 1.11 (0.64, 1.94) | 0.99 (0.56, 1.74) | |||||
| KLF13 rs2241779 | .62 | .21 | .019 | .57 | .20 | |||||||||
| C/C | 30 | 14 (56%) | 11 (44%) | 3.0 (1.8, 4.6) | 1 (Reference) | 1 (Reference) | 10.3 (6.1, 15.5) | 1 (Reference) | 1 (Reference) | |||||
| C/A | 33 | 12 (46%) | 14 (54%) | 1.8 (1.5, 2.3) | 1.48 (0.89, 2.45) | 2.13 (1.24, 3.65) | 8.1 (5.1, 12.0) | 1.37 (0.74, 2.55) | 1.78 (0.94, 3.40) | |||||
| A/A | 15 | 5 (38%) | 8 (62%) | 2.0 (1.6, 2.7) | 1.49 (0.79, 2.80) | 1.83 (0.95, 3.50) | 7.9 (3.1, 29.9) | 1.32 (0.61, 2.85) | 1.54 (0.71, 3.37) | |||||
| .44 | .079 | .006 | .29 | .081 | ||||||||||
| C/C | 30 | 14 (56%) | 11 (44%) | 3.0 (1.8, 4.6) | 1 (Reference) | 1 (Reference) | 10.3 (6.1, 15.5) | 1 (Reference) | 1 (Reference) | |||||
| Any A | 48 | 17 (44%) | 22 (56%) | 1.9 (1.7, 2.3) | 1.48 (0.93, 2.36) | 2.02 (1.23, 3.33) | 7.9 (5.2, 11.8) | 1.35 (0.76, 2.40) | 1.70 (0.94, 3.07) | |||||
| CCL5 rs2280789 | .55 | .27 | .17 | .29 | .42 | |||||||||
| A/A | 106 | 38 (37%) | 64 (63%) | 2.0 (1.8, 2.3) | 1 (Reference) | 1 (Reference) | 5.9 (4.7, 7.8) | 1 (Reference) | 1 (Reference) | |||||
| A/Ga | 41 | 12 (32%) | 26 (68%) | 2.1 (1.9, 2.8) | 0.82 (0.57, 1.19) | 0.76 (0.52, 1.12) | 8.0 (4.3, 10.1) | 0.82 (0.56, 1.20) | 0.85 (0.57, 1.26) | |||||
| G/Ga | 2 | 0 (0%) | 2 (100%) | |||||||||||
| CCL5 rs3817655 | .42 | .42 | .10 | .51 | .34 | |||||||||
| A/A | 98 | 35 (37%) | 60 (63%) | 2.0 (1.8, 2.3) | 1 (Reference) | 1 (Reference) | 6.3 (5.0, 7.9) | 1 (Reference) | 1 (Reference) | |||||
| A/Ta | 47 | 15 (32%) | 32 (68%) | 2.2 (1.9, 2.5) | 0.87 (0.62, 1.23) | 0.74 (0.51, 1.06) | 6.0 (4.3, 9.7) | 0.89 (0.62, 1.27) | 0.83 (0.57, 1.21) | |||||
| T/Ta | 4 | 0 | 4 (100%) | |||||||||||
| CCR5 rs1799988 | .32 | .40 | .076 | .66 | .21 | |||||||||
| T/T | 52 | 13 (27%) | 36 (73%) | 2.1 (1.8, 2.3) | 1 (Reference) | 1 (Reference) | 5.5 (4.0, 7.8) | 1 (Reference) | 1 (Reference) | |||||
| T/C | 64 | 24 (39%) | 37 (61%) | 2.1 (1.8, 3.7) | 0.78 (0.54, 1.13) | 0.64 (0.43, 0.94) | 8.9 (5.7, 10.5) | 0.84 (0.57, 1.24) | 0.70 (0.47, 1.04) | |||||
| C/C | 34 | 13 (39%) | 20 (61%) | 1.9 (1.8, 3.4) | 0.89 (0.57, 1.37) | 0.76 (0.49, 1.18) | 5.6 (3.4, 8.7) | 0.93 (0.59, 1.47) | 0.87 (0.54, 1.40) | |||||
| .14 | .22 | .032 | .44 | .12 | ||||||||||
| T/T | 52 | 13 (27%) | 36 (73%) | 2.1 (1.8, 2.3) | 1 (Reference) | 1 (Reference) | 5.5 (4.0, 7.8) | 1 (Reference) | 1 (Reference) | |||||
| Any C | 98 | 37 (39%) | 57 (61%) | 2.1 (1.8, 2.7) | 0.81 (0.58, 1.15) | 0.68 (0.48, 0.97) | 7.1 (5.1, 9.5) | 0.87 (0.61, 1.24) | 0.75 (0.52, 1.08) | |||||
| CCL3 rs1130371 | .10 | .002 | .027 | .004 | .047 | |||||||||
| G/G | 95 | 37 (40%) | 55 (60%) | 2.3 (2.1, 3.4) | 1 (Reference) | 1 (Reference) | 7.9 (5.9, 9.6) | 1 (Reference) | 1 (Reference) | |||||
| Any A | 55 | 13 (25%) | 38 (75%) | 1.8 (1.7, 2.0) | 1.66 (1.18, 2.33) | 1.50 (1.05, 2.15) | 4.4 (2.7, 6.4) | 1.65 (1.16, 2.34) | 1.44 (1.01, 2.07) | |||||
| CCL4 rs1634517 | .077 | .003 | .040 | .004 | .034 | |||||||||
| C/C | 95 | 37 (41%) | 54 (59%) | 2.3 (2.1, 3.6) | 1 (Reference) | 1 (Reference) | 7.9 (5.9, 9.6) | 1 (Reference) | 1 (Reference) | |||||
| C/A | 48 | 10 (22%) | 35 (78%) | 1.8 (1.7, 2.0) | 1.73 (1.21, 2.48) | 1.58 (1.08, 2.30) | 4.9 (2.7, 7.6) | 1.56 (1.08, 2.24) | 1.37 (0.94, 1.99) | |||||
| A/A | 7 | 3 (43%) | 4 (57%) | 1.7 (0.9, 3.1) | 1.78 (0.82, 3.89) | 1.72 (0.78, 3.78) | 3.4 (1.0, 5.9) | 2.67 (1.22, 5.86) | 2.53 (1.15, 5.56) | |||||
| .070 | <.001 | .012 | .004 | .041 | ||||||||||
| C/C | 95 | 37 (41%) | 54 (59%) | 2.3 (2.1, 3.6) | 1 (Reference) | 1 (Reference) | 7.9 (5.9, 9.6) | 1 (Reference) | 1 (Reference) | |||||
| Any A | 55 | 13 (25%) | 39 (75%) | 1.8 (1.7, 2.0) | 1.74 (1.24, 2.45) | 1.59 (1.11, 2.29) | 4.4 (2.7, 6.4) | 1.65 (1.16, 2.34) | 1.46 (1.01, 2.09) | |||||
| KLF13 rs2241779 | .21 | .28 | .17 | .88 | .51 | |||||||||
| C/C | 33 | 13 (43%) | 17 (57%) | 2.3 (1.8, 4.1) | 1 (Reference) | 1 (Reference) | 8.0 (3.6, 10.0) | 1 (Reference) | 1 (Reference) | |||||
| A/C | 72 | 19 (28%) | 50 (72%) | 1.9 (1.8, 2.1) | 1.38 (0.91, 2.09) | 1.37 (0.90, 2.09) | 5.9 (4.5, 7.8) | 1.06 (0.69, 1.63) | 1.05 (0.68, 1.62) | |||||
| A/A | 44 | 17 (40%) | 26 (60%) | 2.3 (1.9, 2.8) | 1.15 (0.73, 1.82) | 0.99 (0.62,1.58) | 5.7 (4.4, 9.5) | 0.96 (0.60, 1.53) | 0.83 (0.51, 1.34) | |||||
| .28 | .21 | .38 | .93 | .83 | ||||||||||
| C/C | 33 | 13 (43%) | 17 (57%) | 2.3 (1.8, 4.1) | 1 (Reference) | 1 (Reference) | 8.0 (3.6, 10.0) | 1 (Reference) | 1 (Reference) | |||||
| Any A | 116 | 36 (32%) | 76 (68%) | 2.0 (1.8, 2.3) | 1.28 (0.86, 1.90) | 1.20 (0.80, 1.78) | 5.9 (4.7, 7.8) | 1.02 (0.68, 1.52) | 0.96 (0.64, 1.44) | |||||
Abbreviations: PD = progressive disease; PR = partial response; SD = stable disease.
P values<.05 were shown in bold.
*
P value was based on the Fisher’s exact test for response, log-rank test in the univariate analysis
†
() and Wald test in the multivariable analysis within Cox regression model
‡
() adjusted for liver metastasis and LN metastasis in the evaluation cohort; time to REGO started (<18 vs ≥18 months), ECOG performance status (0 vs 1 or 2), primary tumor resection (yes vs no), and Kohne score (low-intermediate vs high) in the validation cohort.
a
Grouped together for estimate of HR.