Table 2.
Genetic polymorphisms in association with disease-free and overall survival.
| Gene, SNP | n, (%) | Disease-free survival (DFS) | Overall survival (OS) | |||||
|---|---|---|---|---|---|---|---|---|
| Median DFS, m (95% CI) | Hazard ratio (95% CI) | p† | Median OS, m (95% CI) | Hazard ratio (95% CI) | p† | |||
| VEGF + 936 (C > T, rs3025039) | CC | 76 (67.9) | 13 (5.3–20.7) | 1 (reference) | .157 | 21 (10.0–32.0) | 1 (reference) | .674 |
| CT | 35 (31.3) | 9 (4.0–14.0) | 1.425 (0.855–2.375) | 20 (12.4–27.6) | 1.110 (0.678–1.816) | |||
| TT | 1 (0.9) | |||||||
| EGF + 61 (A > G, rs4444903) | AA | 48 (42.9) | 16 (8.2–23.8) | 1 (reference) | .669 | 21 (5.5–36.5) | 1 (reference) | .753 |
| AG | 64 (57.1) | 10 (5.5–14.5) | 1.111 (0.676–1.826) | 22 (13.8–30.2) | 1.077 (0.674–1.721) | |||
| GG | 0 (0.0) | |||||||
| EGFR-1562 (G > A, rs2227983) | GG | 38 (33.9) | 10 (5.8–14.2) | 1 (reference) | .847 | 22 (7.6–36.4) | 1 (reference) | .262 |
| GA | 45 (40.2) | 16 (8.2–23.8) | 1.013 (0.565–1.815) | 28 (6.8–49.2) | 1.185 (0.645–2.178) | |||
| AA | 27 (24.1) | 8 (.9–15.1) | 1.190 (0.605–2.343) | 13 (7.1–18.9) | 0.737 (0.426–1.277) | |||
| IL-1B +3954 (C > T, rs1143634) | TT | 8 (7.1) | 24 (n.a.) | 1 (reference) | .012 | 44 (3.9–84.0) | 1 (reference) | .034 |
| CT | 31 (27.7) | |||||||
| CC | 73 (65.2) | 9 (5.9–12.1) | 1.983 (1.139–3.453) | 19 (13.0–25.0) | 1.735 (1.043–2.886) | |||
| IL-6-174 (G > C, rs1800795) | GG | 41 (36.6) | 12 (0.0–28.6) | 1 (reference) | .413 | 29 (0.0–69.2) | 1 (reference) | .237 |
| GC | 53 (47.3) | 12 (6.3–17.7) | 1.112 (0.644–1.918) | 18 (10.3–25.7) | 1.537 (0.914–2.587) | |||
| CC | 16 (14.3) | 8 (2.9–13.1) | 1.590 (0.781–3.239) | 22 (13.1–30.9) | 1.465 (0.714–3.004) | |||
| IL-8-251 (T > A, rs4073) | TT | 33 (29.5) | 12 (3.3–20.7) | 1 (reference) | .679 | 40 (14.8–65.2) | 1 (reference) | .026 |
| TA | 53 (47.3) | 12 (7.7–16.3) | 1.203 (0.674–2.149) | 13 (2.7–23.3) | 2.001 (1.144–3.498) | |||
| AA | 20 (17.9) | 8 (0.2–15.8) | 1.339 (0.661–2.714) | 32 (6.3–57.7) | 1.177 (0.566–2.445) | |||
| IL-10-592 (T > G, rs1800872) | TT | 5 (4.5) | 12 (6.9–17.1) | 1 (reference) | .380 | 19 (11.9–26.1) | 1 (reference) | .928 |
| TG | 53 (47.3) | |||||||
| GG | 54 (48.2) | 10 (5.6–14.4) | 1.239 (0.758–2.023) | 22 (15.9–28.1) | 0.979 (0.616–1.557) | |||
| CXCR1 + 860(Ex2) (C > G, rs2234671) | CC | 102 (91.1) | 12 (8.6–15.4) | 1 (reference) | .638 | 20 (16.3–23.7) | 1 (reference) | .662 |
| CG | 10 (8.9) | 7 (1.9–12.1) | 0.789 (0.286–2.175) | 25 (0.0–82.8) | 0.817 (0.353–1.892) | |||
| GG | 0 (0.0) | |||||||
| HIF1α-1772 (C > T, rs11549465) | CC | 88 (78.6) | 11 (8.0–14.0) | 1 (reference) | .461 | 19 (11.3–26.6) | 1 (reference) | .676 |
| CT | 23 (20.5) | 18 (8.1–27.9) | 0.804 (0.443–1.459) | 28 (5.0–51.0) | 0.889 (0.507–1.558) | |||
| TT | 0 (0.0) | |||||||
| PTGS2 (COX2) + 8473 (A > G, rs5275) | AA | 49 (43.8) | 12 (9.2–14.8) | 1 (reference) | .669 | 20 (8.9–31.0) | 1 (reference) | .630 |
| AG | 48 (42.9) | 12 (6.3–17.7) | 0.988 (0.588–1.661) | 25 (11.9–38.1) | 0.891 (0.547–1.451) | |||
| GG | 12 (10.0) | 18 (2.1–33.9) | 0.632 (0.283–1.650) | 29 (0.0–62.9) | 0.694 (0.307–1.567) | |||
| PTGS2 (COX2)-765 (G > C, rs20417) | GG | 81 (72.3) | 11 (6.9–15.1) | 1 (reference) | .993 | 22 (12.9–31.1) | 1 (reference) | .360 |
| GC | 25 (22.3) | 13 (3.8–22.3) | 0.998 (0.578–1.722) | 29 (2.6–55.4) | 0.783 (0.459–1.334) | |||
| CC | 4 (3.5) | |||||||
Based on Cox proportional hazards model, for DFS including: Blood transfusions, microvascular invasion, lymphovascular invasion, lymph node positivity, UICC stage. For OS including: Alkaline phosphatase, hemoglobin, C-reactive protein, blood transfusions, microvascular invasion, lymphovascular invasion, lymph node positivity, UICC stage, comprehensive complication index and hospitalization. Also see Supplementary Table 2 and 3.
n.a. estimates not reached, CI confidence interval, CXCR chemokine receptor, EGF epidermal growth factor, EGFR epidermal growth factor receptor, HIF-1α hypoxia-inducing factor alpha, IL interleukin, PTGS prostaglandin-endoperoxide synthase 2, SNP single-nucleotide polymorphism, VEGF vascular endothelial growth factor, iCCA intrahepatic cholangiocarcinoma.
†Based on log-rank test.
$Significances given for the T/A vs. T/T groups and for the “2 unfavorable” vs. “0 unfavorable” groups.
Significant values are in bold.