Etoposide genes significantly associated with at least 2 time exposures and at least 1 clinical outcome
| Gene . | . | Etoposide . | Clinical . | EFS . | OS . | MRD1 . | RR . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Unadjusted . | Risk-adjusted . | Unadjusted . | Risk-adjusted . | Unadjusted . | Risk-adjusted . | Unadjusted . | Risk-adjusted . | ||||
| ABCC1 | ATP-binding cassette subfamily C member 1 | EtoRGs | Unfavorable | 1.77 (1.19-2.63)∗∗ | 1.58 (1.05-2.36)∗ | 1.89 (1.18-3.02)∗∗ | 1.6 (0.98-2.59) | 2.99 (1.66-5.39)∗∗∗ | 2.33 (1.23-4.42)∗∗ | 1.47 (0.82-2.63) | 1.26 (0.72-2.21) |
| PRKDC | Protein kinase, DNA-activated, catalytic subunit | EtoRGs | Unfavorable | 1.39 (1.07-1.82)∗ | 1.37 (1.05-1.8)∗ | 1.65 (1.19-2.28)∗∗ | 1.66 (1.19-2.32)∗∗ | 1.19 (0.85-1.67) | 1.19 (0.81-1.75) | 1.39 (1.01-1.9)∗ | 1.35 (0.98-1.87) |
| RAD54L2 | DNA repair and recombination protein RAD54-like2 | EtoRGs | Unfavorable | 1.65 (1.17-2.33)∗∗ | 1.66 (1.18-2.34)∗∗ | 1.74 (1.19-2.54)∗∗ | 1.73 (1.19-2.52)∗∗ | 1.7 (1.04-2.78)∗ | 1.86 (1.06-3.24)∗ | 1.65 (1.04-2.64)∗ | 1.6 (1-2.55)∗ |
| ZNF451 | Zinc-finger protein 451 | EtoRGs | Unfavorable | 1.23 (0.87-1.73) | 1.14 (0.82-1.58) | 1.24 (0.83-1.85) | 1.13 (0.77-1.65) | 1.7 (1.06-2.73)∗ | 1.69 (1.02-2.8)∗ | 1.12 (0.74-1.7) | 1.04 (0.71-1.54) |
| CCNF | Cyclin F | EtoRGs | Favorable | 0.75 (0.55-1.01) | 0.67 (0.5-0.9)∗∗ | 0.83 (0.59-1.17) | 0.76 (0.55-1.05) | 1.04 (0.68-1.57) | 0.85 (0.54-1.35) | 0.74 (0.48-1.14) | 0.66 (0.45-0.98)∗ |
| NHEJ1 | Nonhomologous end joining factor 1 | EtoRGs | Favorable | 0.8 (0.49-1.3) | 0.64 (0.39-1.05) | 0.95 (0.54-1.69) | 0.81 (0.47-1.4) | 0.98 (0.51-1.88) | 0.73 (0.36-1.51) | 0.6 (0.34-1.06) | 0.47 (0.26-0.85)∗ |
| CBFB | Core-binding factor subunit beta | EtoSGs | Unfavorable | 1.88 (0.99-3.56) | 1.45 (0.73-2.91) | 1.64 (0.79-3.39) | 1.16 (0.53-2.56) | 2.73 (1.18-6.3)∗ | 1.58 (0.6-4.13) | 1.5 (0.64-3.5) | 0.94 (0.36-2.43) |
| IMPDH2 | Inosine monophosphate dehydrogenase 2 | EtoSGs | Unfavorable | 1.45 (0.93-2.24) | 1.32 (0.87-2) | 1.84 (1.08-3.14)∗ | 1.63 (0.99-2.69) | 1.72 (0.96-3.09) | 1.54 (0.79-3) | 1 (0.54-1.85) | 0.91 (0.52-1.59) |
| RUNX1 | RUNX family transcription factor 1 | EtoSGs | Unfavorable | 1.19 (0.94-1.51) | 1.29 (1.02-1.63)∗ | 1.31 (0.99-1.75) | 1.44 (1.08-1.92)∗ | 1.01 (0.75-1.36) | 1.08 (0.77-1.52) | 0.99 (0.76-1.29) | 1.06 (0.81-1.38) |
| SLC25A32 | Solute carrier family 25 member 32 | EtoSGs | Unfavorable | 1.55 (0.78-3.08) | 2.47 (1.2-5.11)∗ | 1.47 (0.67-3.2) | 2.32 (1.06-5.06)∗ | 0.85 (0.38-1.9) | 1.64 (0.65-4.14) | 1.89 (0.76-4.72) | 2.95 (1.18-7.37)∗ |
| TARDBP | TAR DNA-binding protein | EtoSGs | Unfavorable | 1.52 (0.85-2.74) | 1.65 (0.89-3.04) | 1.91 (0.93-3.9) | 2.41 (1.12-5.18)∗ | 1.54 (0.71-3.35) | 1.73 (0.68-4.38) | 1.24 (0.68-2.24) | 1.23 (0.64-2.38) |
| ADRM1 | Adhesion regulating molecule 1 | EtoSGs | Favorable | 0.84 (0.49-1.45) | 1 (0.54-1.83) | 0.78 (0.4-1.5) | 0.89 (0.42-1.87) | 1.25 (0.62-2.53) | 2.02 (0.86-4.78) | 0.48 (0.27-0.85)∗ | 0.53 (0.28-1.03) |
| ALDOA | Aldolase, fructose-bisphosphate A | EtoSGs | Favorable | 0.83 (0.56-1.22) | 0.9 (0.6-1.36) | 0.73 (0.48-1.11) | 0.77 (0.49-1.2) | 0.94 (0.5-1.77) | 1.19 (0.58-2.46) | 0.7 (0.55-0.9)∗∗ | 0.77 (0.56-1.05) |
| CKS1B | CDC28 protein kinase regulatory subunit 1B | EtoSGs | Favorable | 0.62 (0.36-1.07) | 0.6 (0.36-1.01) | 0.39 (0.21-0.72)∗∗ | 0.39 (0.21-0.71)∗∗ | 1.02 (0.48-2.17) | 0.96 (0.41-2.24) | 0.8 (0.39-1.67) | 0.78 (0.41-1.49) |
| CTBP1 | C-terminal binding protein 1 | EtoSGs | Favorable | 0.73 (0.4-1.32) | 0.66 (0.36-1.22) | 0.53 (0.27-1.03) | 0.45 (0.23-0.89)∗ | 1.63 (0.72-3.67) | 1.53 (0.61-3.84) | 0.88 (0.39-1.97) | 0.81 (0.36-1.82) |
| HSD17B12 | Hydroxysteroid 17-beta dehydrogenase 12 | EtoSGs | Favorable | 0.65 (0.37-1.15) | 0.69 (0.39-1.2) | 0.43 (0.23-0.82)∗∗ | 0.47 (0.26-0.86)∗ | 1.25 (0.59-2.66) | 1.38 (0.59-3.25) | 0.56 (0.27-1.15) | 0.62 (0.31-1.23) |
| HYPK | Huntingtin interacting protein K | EtoSGs | Favorable | 0.62 (0.32-1.2) | 0.64 (0.32-1.28) | 0.44 (0.22-0.86)∗ | 0.44 (0.21-0.9)∗ | 0.61 (0.21-1.78) | 0.79 (0.25-2.53) | 0.81 (0.32-2.06) | 0.93 (0.31-2.73) |
| MYB | MYB proto-oncogene, transcription factor | EtoSGs | Favorable | 0.81 (0.55-1.18) | 0.71 (0.48-1.04) | 0.75 (0.5-1.14) | 0.66 (0.43-1) | 0.97 (0.59-1.61) | 0.77 (0.43-1.36) | 0.71 (0.43-1.17) | 0.6 (0.38-0.96)∗ |
| PPP2R1A | Protein phosphatase 2 scaffold subunit Aalpha | EtoSGs | Favorable | 0.93 (0.53-1.63) | 1.03 (0.58-1.83) | 0.96 (0.48-1.91) | 1.1 (0.53-2.29) | 0.77 (0.36-1.64) | 0.95 (0.41-2.19) | 0.57 (0.37-0.87)∗∗ | 0.61 (0.4-0.94)∗ |
| RAD23B | RAD23 homolog B, nucleotide excision repair protein | EtoSGs | Favorable | 0.43 (0.24-0.78)∗∗ | 0.52 (0.29-0.95)∗ | 0.84 (0.43-1.62) | 1.13 (0.58-2.21) | 0.37 (0.16-0.86)∗ | 0.55 (0.22-1.39) | 0.34 (0.16-0.73)∗∗ | 0.45 (0.21-0.96)∗ |
| RPE | Ribulose-5-phosphate-3-epimerase | EtoSGs | Favorable | 0.76 (0.59-0.99)∗ | 0.72 (0.55-0.93)∗ | 0.69 (0.51-0.93)∗ | 0.64 (0.47-0.87)∗∗ | 1.02 (0.71-1.47) | 0.95 (0.62-1.44) | 0.85 (0.63-1.16) | 0.79 (0.58-1.09) |
| SEC23B | SEC23 homolog B, COPII coat complex component | EtoSGs | Favorable | 0.6 (0.32-1.11) | 0.51 (0.28-0.95)∗ | 0.65 (0.31-1.36) | 0.55 (0.27-1.14) | 1.08 (0.46-2.52) | 0.86 (0.33-2.25) | 0.95 (0.42-2.16) | 0.8 (0.37-1.73) |
| SKP2 | S-phase kinase associated protein 2 | EtoSGs | Favorable | 0.77 (0.57-1.06) | 0.75 (0.55-1.03) | 0.71 (0.49-1.01) | 0.71 (0.49-1.02) | 0.91 (0.6-1.37) | 0.88 (0.55-1.4) | 0.65 (0.43-0.98)∗ | 0.61 (0.41-0.92)∗ |
| TKT | Transketolase | EtoSGs | Favorable | 0.71 (0.54-0.94)∗ | 0.81 (0.6-1.09) | 0.68 (0.49-0.95)∗ | 0.79 (0.55-1.14) | 0.57 (0.35-0.9)∗ | 0.74 (0.44-1.23) | 0.56 (0.44-0.72)∗∗∗ | 0.64 (0.49-0.83)∗∗ |
| TOP2A | DNA TOP2 alpha | EtoSGs | Favorable | 0.73 (0.59-0.9)∗∗ | 0.69 (0.56-0.84)∗∗∗ | 0.71 (0.56-0.91)∗∗ | 0.67 (0.53-0.85)∗∗∗ | 0.95 (0.72-1.26) | 0.84 (0.61-1.15) | 0.85 (0.65-1.12) | 0.8 (0.63-1.03) |
| TUT7 | Terminal uridylyl transferase 7 | EtoSGs | Favorable | 0.79 (0.58-1.08) | 0.72 (0.53-0.97)∗ | 0.77 (0.54-1.11) | 0.69 (0.49-0.97)∗ | 0.98 (0.62-1.55) | 0.82 (0.48-1.38) | 0.93 (0.62-1.4) | 0.84 (0.59-1.19) |
| Gene . | . | Etoposide . | Clinical . | EFS . | OS . | MRD1 . | RR . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Unadjusted . | Risk-adjusted . | Unadjusted . | Risk-adjusted . | Unadjusted . | Risk-adjusted . | Unadjusted . | Risk-adjusted . | ||||
| ABCC1 | ATP-binding cassette subfamily C member 1 | EtoRGs | Unfavorable | 1.77 (1.19-2.63)∗∗ | 1.58 (1.05-2.36)∗ | 1.89 (1.18-3.02)∗∗ | 1.6 (0.98-2.59) | 2.99 (1.66-5.39)∗∗∗ | 2.33 (1.23-4.42)∗∗ | 1.47 (0.82-2.63) | 1.26 (0.72-2.21) |
| PRKDC | Protein kinase, DNA-activated, catalytic subunit | EtoRGs | Unfavorable | 1.39 (1.07-1.82)∗ | 1.37 (1.05-1.8)∗ | 1.65 (1.19-2.28)∗∗ | 1.66 (1.19-2.32)∗∗ | 1.19 (0.85-1.67) | 1.19 (0.81-1.75) | 1.39 (1.01-1.9)∗ | 1.35 (0.98-1.87) |
| RAD54L2 | DNA repair and recombination protein RAD54-like2 | EtoRGs | Unfavorable | 1.65 (1.17-2.33)∗∗ | 1.66 (1.18-2.34)∗∗ | 1.74 (1.19-2.54)∗∗ | 1.73 (1.19-2.52)∗∗ | 1.7 (1.04-2.78)∗ | 1.86 (1.06-3.24)∗ | 1.65 (1.04-2.64)∗ | 1.6 (1-2.55)∗ |
| ZNF451 | Zinc-finger protein 451 | EtoRGs | Unfavorable | 1.23 (0.87-1.73) | 1.14 (0.82-1.58) | 1.24 (0.83-1.85) | 1.13 (0.77-1.65) | 1.7 (1.06-2.73)∗ | 1.69 (1.02-2.8)∗ | 1.12 (0.74-1.7) | 1.04 (0.71-1.54) |
| CCNF | Cyclin F | EtoRGs | Favorable | 0.75 (0.55-1.01) | 0.67 (0.5-0.9)∗∗ | 0.83 (0.59-1.17) | 0.76 (0.55-1.05) | 1.04 (0.68-1.57) | 0.85 (0.54-1.35) | 0.74 (0.48-1.14) | 0.66 (0.45-0.98)∗ |
| NHEJ1 | Nonhomologous end joining factor 1 | EtoRGs | Favorable | 0.8 (0.49-1.3) | 0.64 (0.39-1.05) | 0.95 (0.54-1.69) | 0.81 (0.47-1.4) | 0.98 (0.51-1.88) | 0.73 (0.36-1.51) | 0.6 (0.34-1.06) | 0.47 (0.26-0.85)∗ |
| CBFB | Core-binding factor subunit beta | EtoSGs | Unfavorable | 1.88 (0.99-3.56) | 1.45 (0.73-2.91) | 1.64 (0.79-3.39) | 1.16 (0.53-2.56) | 2.73 (1.18-6.3)∗ | 1.58 (0.6-4.13) | 1.5 (0.64-3.5) | 0.94 (0.36-2.43) |
| IMPDH2 | Inosine monophosphate dehydrogenase 2 | EtoSGs | Unfavorable | 1.45 (0.93-2.24) | 1.32 (0.87-2) | 1.84 (1.08-3.14)∗ | 1.63 (0.99-2.69) | 1.72 (0.96-3.09) | 1.54 (0.79-3) | 1 (0.54-1.85) | 0.91 (0.52-1.59) |
| RUNX1 | RUNX family transcription factor 1 | EtoSGs | Unfavorable | 1.19 (0.94-1.51) | 1.29 (1.02-1.63)∗ | 1.31 (0.99-1.75) | 1.44 (1.08-1.92)∗ | 1.01 (0.75-1.36) | 1.08 (0.77-1.52) | 0.99 (0.76-1.29) | 1.06 (0.81-1.38) |
| SLC25A32 | Solute carrier family 25 member 32 | EtoSGs | Unfavorable | 1.55 (0.78-3.08) | 2.47 (1.2-5.11)∗ | 1.47 (0.67-3.2) | 2.32 (1.06-5.06)∗ | 0.85 (0.38-1.9) | 1.64 (0.65-4.14) | 1.89 (0.76-4.72) | 2.95 (1.18-7.37)∗ |
| TARDBP | TAR DNA-binding protein | EtoSGs | Unfavorable | 1.52 (0.85-2.74) | 1.65 (0.89-3.04) | 1.91 (0.93-3.9) | 2.41 (1.12-5.18)∗ | 1.54 (0.71-3.35) | 1.73 (0.68-4.38) | 1.24 (0.68-2.24) | 1.23 (0.64-2.38) |
| ADRM1 | Adhesion regulating molecule 1 | EtoSGs | Favorable | 0.84 (0.49-1.45) | 1 (0.54-1.83) | 0.78 (0.4-1.5) | 0.89 (0.42-1.87) | 1.25 (0.62-2.53) | 2.02 (0.86-4.78) | 0.48 (0.27-0.85)∗ | 0.53 (0.28-1.03) |
| ALDOA | Aldolase, fructose-bisphosphate A | EtoSGs | Favorable | 0.83 (0.56-1.22) | 0.9 (0.6-1.36) | 0.73 (0.48-1.11) | 0.77 (0.49-1.2) | 0.94 (0.5-1.77) | 1.19 (0.58-2.46) | 0.7 (0.55-0.9)∗∗ | 0.77 (0.56-1.05) |
| CKS1B | CDC28 protein kinase regulatory subunit 1B | EtoSGs | Favorable | 0.62 (0.36-1.07) | 0.6 (0.36-1.01) | 0.39 (0.21-0.72)∗∗ | 0.39 (0.21-0.71)∗∗ | 1.02 (0.48-2.17) | 0.96 (0.41-2.24) | 0.8 (0.39-1.67) | 0.78 (0.41-1.49) |
| CTBP1 | C-terminal binding protein 1 | EtoSGs | Favorable | 0.73 (0.4-1.32) | 0.66 (0.36-1.22) | 0.53 (0.27-1.03) | 0.45 (0.23-0.89)∗ | 1.63 (0.72-3.67) | 1.53 (0.61-3.84) | 0.88 (0.39-1.97) | 0.81 (0.36-1.82) |
| HSD17B12 | Hydroxysteroid 17-beta dehydrogenase 12 | EtoSGs | Favorable | 0.65 (0.37-1.15) | 0.69 (0.39-1.2) | 0.43 (0.23-0.82)∗∗ | 0.47 (0.26-0.86)∗ | 1.25 (0.59-2.66) | 1.38 (0.59-3.25) | 0.56 (0.27-1.15) | 0.62 (0.31-1.23) |
| HYPK | Huntingtin interacting protein K | EtoSGs | Favorable | 0.62 (0.32-1.2) | 0.64 (0.32-1.28) | 0.44 (0.22-0.86)∗ | 0.44 (0.21-0.9)∗ | 0.61 (0.21-1.78) | 0.79 (0.25-2.53) | 0.81 (0.32-2.06) | 0.93 (0.31-2.73) |
| MYB | MYB proto-oncogene, transcription factor | EtoSGs | Favorable | 0.81 (0.55-1.18) | 0.71 (0.48-1.04) | 0.75 (0.5-1.14) | 0.66 (0.43-1) | 0.97 (0.59-1.61) | 0.77 (0.43-1.36) | 0.71 (0.43-1.17) | 0.6 (0.38-0.96)∗ |
| PPP2R1A | Protein phosphatase 2 scaffold subunit Aalpha | EtoSGs | Favorable | 0.93 (0.53-1.63) | 1.03 (0.58-1.83) | 0.96 (0.48-1.91) | 1.1 (0.53-2.29) | 0.77 (0.36-1.64) | 0.95 (0.41-2.19) | 0.57 (0.37-0.87)∗∗ | 0.61 (0.4-0.94)∗ |
| RAD23B | RAD23 homolog B, nucleotide excision repair protein | EtoSGs | Favorable | 0.43 (0.24-0.78)∗∗ | 0.52 (0.29-0.95)∗ | 0.84 (0.43-1.62) | 1.13 (0.58-2.21) | 0.37 (0.16-0.86)∗ | 0.55 (0.22-1.39) | 0.34 (0.16-0.73)∗∗ | 0.45 (0.21-0.96)∗ |
| RPE | Ribulose-5-phosphate-3-epimerase | EtoSGs | Favorable | 0.76 (0.59-0.99)∗ | 0.72 (0.55-0.93)∗ | 0.69 (0.51-0.93)∗ | 0.64 (0.47-0.87)∗∗ | 1.02 (0.71-1.47) | 0.95 (0.62-1.44) | 0.85 (0.63-1.16) | 0.79 (0.58-1.09) |
| SEC23B | SEC23 homolog B, COPII coat complex component | EtoSGs | Favorable | 0.6 (0.32-1.11) | 0.51 (0.28-0.95)∗ | 0.65 (0.31-1.36) | 0.55 (0.27-1.14) | 1.08 (0.46-2.52) | 0.86 (0.33-2.25) | 0.95 (0.42-2.16) | 0.8 (0.37-1.73) |
| SKP2 | S-phase kinase associated protein 2 | EtoSGs | Favorable | 0.77 (0.57-1.06) | 0.75 (0.55-1.03) | 0.71 (0.49-1.01) | 0.71 (0.49-1.02) | 0.91 (0.6-1.37) | 0.88 (0.55-1.4) | 0.65 (0.43-0.98)∗ | 0.61 (0.41-0.92)∗ |
| TKT | Transketolase | EtoSGs | Favorable | 0.71 (0.54-0.94)∗ | 0.81 (0.6-1.09) | 0.68 (0.49-0.95)∗ | 0.79 (0.55-1.14) | 0.57 (0.35-0.9)∗ | 0.74 (0.44-1.23) | 0.56 (0.44-0.72)∗∗∗ | 0.64 (0.49-0.83)∗∗ |
| TOP2A | DNA TOP2 alpha | EtoSGs | Favorable | 0.73 (0.59-0.9)∗∗ | 0.69 (0.56-0.84)∗∗∗ | 0.71 (0.56-0.91)∗∗ | 0.67 (0.53-0.85)∗∗∗ | 0.95 (0.72-1.26) | 0.84 (0.61-1.15) | 0.85 (0.65-1.12) | 0.8 (0.63-1.03) |
| TUT7 | Terminal uridylyl transferase 7 | EtoSGs | Favorable | 0.79 (0.58-1.08) | 0.72 (0.53-0.97)∗ | 0.77 (0.54-1.11) | 0.69 (0.49-0.97)∗ | 0.98 (0.62-1.55) | 0.82 (0.48-1.38) | 0.93 (0.62-1.4) | 0.84 (0.59-1.19) |
EFS and OS were fitted using Cox proportional-hazards model to estimate HR and 95% CI. MRD1 was fitted using logistic regression model to estimate OR and 95% CI. RR was fitted using the methods of Gray for estimating HR, controlling for competing risks.
CI, confidence interval.
∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .001.