Table 2.
Association of genetic variants of autophagy core genes with primary resistance or acquired resistance of gefitinib.
| Genes | SNPs | Genotypes | Patients No. (%) | Primary resistance | Acquired resistance | |||
|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | |||||
| ATG5 | rs510432 | GG | 105 | Reference | Reference | |||
| 43(40.95) | ||||||||
| GA | 41(39.05) | 0.54 (0.25-1.15) | 0.107 | 0.95 (0.55-1.62) | 0.838 | |||
| AA | 21(20.00) | 0.34 (0.13-0.93) | 0.035 | 1.28 (0.67-2.46) | 0.453 | |||
| GA + AA | 62(59.05) | 0.45 (0.24-0.87) | 0.017 | 1.05 (0.65-1.69) | 0.848 | |||
| ATG5 | rs688810 | TT | 106 | Reference | Reference | |||
| 41(38.68) | ||||||||
| TC | 43(40.57) | 1.67 (0.77-3.63) | 0.194 | 0.99 (0.52-1.89) | 0.972 | |||
| CC | 22(20.75) | 1.76 (0.74-4.20) | 0.200 | 0.96 (0.42-2.17) | 0.912 | |||
| TC + CC | 65(61.32) | 1.70 (0.85-3.41) | 0.132 | 1.03 (0.57-1.85) | 0.920 | |||
| ATG10 | rs10036653 | AA | 107 | Reference | Reference | |||
| 40(37.38) | ||||||||
| AT | 52(48.60) | 0.74 (0.35-1.54) | 0.418 | 0.61(0.32-1.18) | 0.142 | |||
| TT | 15(14.02) | 0.66 (0.23-1.86) | 0.432 | 0.39 (0.13-1.20) | 0.101 | |||
| AT + TT | 67(62.62) | 0.77 (0.40-1.50) | 0.446 | 0.59 (0.32-1.10) | 0.099 | |||
| ATG10 | rs1864182 | TT | 113 | Reference | Reference | |||
| 96(84.96) | ||||||||
| TG | 16(14.16) | 2.07 (0.91-4.72) | 0.082 | 0.30 (0.09-0.97) | 0.044 | |||
| GG | 1(0.88) | N.C. | N.C. | N.C. | N.C. | |||
| TG + GG | 17(15.04) | 2.27 (1.04-4.97) | 0.040 | 0.30 (0.09-0.97) | 0.044 | |||
| Genes | SNPs | Genotypes | Patients with EGFR mutation No. (%) | Primary resistance of patients with EGFR mutations | Acquired resistance of patients with EGFR mutations | |||
| HR (95% CI) | P | HR (95% CI) | P | |||||
| ATG5 | rs510432 | GG | 78 | Reference | Reference | |||
| 33(42.31) | ||||||||
| GA | 28(35.90) | 0.56 (0.22-1.41) | 0.217 | 0.65 (0.26-1.62) | 0.353 | |||
| AA | 17(21.79) | 0.24 (0.07-0.85) | 0.026 | 0.77 (0.29-2.05) | 0.605 | |||
| GA + AA | 45(57.69) | 0.39 (0.18-0.85) | 0.018 | 0.74 (0.34-1.60) | 0.448 | |||
| ATG5 | rs688810 | TT | 80 | Reference | Reference | |||
| 31(38.75) | ||||||||
| TC | 31(38.75) | 2.89 (1.05-8.01) | 0.041 | 0.94 (0.45-1.99) | 0.877 | |||
| CC | 18(22.50) | 3.02 (1.11-8.19) | 0.030 | 1.21 (0.46-3.23) | 0.700 | |||
| TC + CC | 49(61.25) | 3.01 (1.26-7.22) | 0.014 | 1.07 (0.54-2.10) | 0.854 | |||
| ATG10 | rs10036653 | AA | 80 | Reference | Reference | |||
| 28(35.00) | ||||||||
| AT | 43(53.75) | 0.66 (0.29-1.53) | 0.332 | 0.41 (0.21-0.83) | 0.013 | |||
| TT | 9(11.25) | 0.60 (0.17-2.12) | 0.423 | 0.29 (0.06-1.38) | 0.120 | |||
| AT + TT | 52(65.00) | 0.66 (0.31-1.40) | 0.278 | 0.37 (0.19-0.72) | 0.004 | |||
| ATG10 | rs1864182 | TT | 81 | Reference | Reference | |||
| 70(86.42) | ||||||||
| TG | 10(12.35) | 1.75 (0.63-4.87) | 0.283 | 0.55 (0.17-1.81) | 0.323 | |||
| GG | 1(1.23) | N.C. | N.C. | N.C. | N.C. | |||
| TG + GG | 11(13.58) | 2.00 (0.78-5.15) | 0.149 | 0.55 (0.17-1.81) | 0.323 | |||
Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SNPs and geifitinib-resistance were estimated by Cox regression adjusted by sex, age, smoking status, ECGO and stages. N.C., not calculated.