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Supplementary Table S4: Global List of Studied Associations for Chl Prognosis and Treatment Response

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Supplementary Table S4: Global List of Studied Associations for Chl Prognosis and Treatment Response Supplementary Table S4: Global list of studied associations for cHL prognosis and treatment response. Genes SNP Allele comparison Patients Endpoint results Treatment Statistics HR/RR (95% CI) Comments Results References ABVD/ChIVPP (70%), BEACOPP (11%), CHOP/COP/CHOEP ABCC2 rs17222723 TA/AA vs TT 223 EFS/OS (ns) ns Not significant 69 (19%) + Radiotherapy CCL17 rs223828 TC/TT vs CC 437 PFS (ns) Newly diagnosed (34%), NA (66%) ns Not significant s9 CYP3A4 rs2740574 AG/GG vs AA 310 OS/FFP/FFTF (ns) ABVD(66%), EBVP (22%), BEACOPP (12%) ns Not significant 68 FAM179B rs1053667 CC vs TT 103 DFS/OS (ns) ABVD (52%), MOPPABVD (38%) ns Not significant 71 FCGR2A rs1801274 AA vs GG/GA 239 EFS Newly diagnosed ns Not significant 34 FCGR3A rs396991 TT vs GG/GT 239 EFS Newly diagnosed ns Not significant 34 ABVD/ChIVPP (70%), BEACOPP (11%), CHOP/COP/CHOEP GSTA1 rs3957357 AG/GG vs AA 224 EFS/OS (ns) ns Not significant 69 (19%) + Radiotherapy BEACOPP (50,5%), MOPP/COPP/ABV (31%), ABVD (16,5%) GSTM1 deletion deletion vs present 125 Adverse DFS p=0.02 5.6 (1.24-25.48) Brazil s10 + Radiotherapy (49%) ABVD/ChIVPP (70%), BEACOPP (11%), CHOP/COP/CHOEP deletion deletion vs present 221 EFS/OS (ns) ns Norway 69 (19%) + Radiotherapy Inconsistent ABVD (52%), Stanford V (32%), ABVD/MOPP (8%), deletion deletion vs present 90 DFS (ns) ns Italy s4 BEACOPP (6%), VEBEP (1%) deletion deletion vs present 312 OS/FFP/FFTF (ns) ABVD(66%), EBVP (22%), BEACOPP (12%) ns France 68 ABVD (55%), Stanford V (29%), MOPP (5%), BEACOPP (9%), GSTP1 rs1695 GA/AA vs GG 97 Favorable FFS p=0.02 0.42 (0.21-0.85) Italy s11 VEBEP (1%) + Radiotherapy (51%) ABVD/ChIVPP (70%), BEACOPP (11%), CHOP/COP/CHOEP rs1695 GA/AA vs GG 222 EFS/OS (ns) ns Norway 69 (19%) + Radiotherapy Inconsistent BEACOPP (50,5%), MOPP/COPP/ABV (31%), ABVD (16,5%) rs1695 GA/AA vs GG 125 DFS (ns) ns Brazil s10 + Radiotherapy (49%) rs947894 GA/GG vs AA 311 OS/FFP/FFTF (ns) ABVD(66%), EBVP (22%), BEACOPP (12%) ns France 68 GSTT1 deletion deletion vs present 312 Favorable OS ABVD(66%), EBVP (22%), BEACOPP (12%) p=0.042 0.43 (0.19-0.97) France 68 BEACOPP (50,5%), MOPP/COPP/ABV (31%), ABVD (16,5%) deletion deletion vs present 125 Favorable OS p=0.05 0.27 (0.07-1.0) Brazil s10 + Radiotherapy (49%) ABVD/ChIVPP (70%), BEACOPP (11%), CHOP/COP/CHOEP Inconsistent deletion deletion vs present 221 EFS/OS (ns) ns Norway 69 (19%) + Radiotherapy ABVD (52%), Stanford V (32%), ABVD/MOPP (8%), deletion deletion vs present 90 DFS (ns) ns Italy s4 BEACOPP (6%), VEBEP (1%) IFNG rs2430561 TA/TT vs AA 439 PFS (ns) Newly diagnosed (34%), NA (66%) ns s9 IL10 rs1800871 TT vs TC/CC 301 Adverse FFTF NA p=0.067 2.7 (0.93-7.81) s12 rs1800871 CT/TT vs CC 685 PFS (ns) Newly diagnosed (34%), NA (66%) ns s9 ABVD (59%), MOPP (9%), Stanford V (18%), BEACOPP rs1800872 AA vs AC/CC 184 Adverse FFTF p=0.001 2.8 (1.53-5.41) rs1800871 is in strong LD with s13 (11%), VEBEP (1%), Radiotherapy (2%) rs1800872 (r2=1) rs1800872 AA vs AC/CC 85 Adverse FFS NA p=0.029 5.4 (1.19-24.6 s14 rs1800872 AA vs AC/CC 301 Adverse FFTF NA p=0.067 2.7 (0.93-7.81) s12 rs1800872 AC/AA vs CC 686 PFS (ns) Newly diagnosed (34%), NA (66%) ns s9 rs1800896 GG vs AG/AA 85 Adverse FFS NA p=0.044 5.9 (1.05-33.2) s14 rs1800896 AA vs AG/GG 301 Adverse FFTF NA p=0.042 2.2 (1.03-4.62) Weak LD for rs1800896 and s12 rs1800896 AG/GG vs AA 184 FFTF (ns) ABVD (59%), MOPP (9%), Stanford V (18%), BEACOPP ns rs1800872 (r2=0.3) / rs1800871 s13 rs1800896 AG/GG vs GG 52 OS (ns) (11%), VEBEP (1%),NA Radiotherapy (2%) ns (r2=0.25) s15 rs1800896 AG/GG vs AA 698 PFS (ns) Newly diagnosed (34%), NA (66%) ns s9 rs6693899 n.d 148 FFTF (ns) ABVD (59%), MOPP (9%), Stanford V (18%), BEACOPP ns s13 Inconsistent rs6693899 CA/AA vs CC 93 FFS (ns) (11%), VEBEP (1%),NA Radiotherapy (2%) ns s14 7400 deletion indel/inin vs deldel 301 FFTF (ns) NA ns s12 rs10494879 CG/GG vs CC 301 FFTF (ns) NA ns s12 rs1800890 AT/TT vs AA 223 EFS/OS (ns) ABVD/ChIVPP (70%), BEACOPP (11%), CHOP/COP/CHOEP ns 69 rs1800890 AT/AA vs TT 182 FFTF (ns) ABVD (59%), MOPP(19%) (9%), + Radiotherapy Stanford V (18%), BEACOPP ns s13 rs1800890 AT/AA vs TT 93 FFS (ns) (11%), VEBEP (1%),NA Radiotherapy (2%) ns None of the SNPs are in LD with s14 rs1800890 AT/AA vs TT 301 FFTF (ns) NA ns rs1800871 / rs1800872 s12 rs1800890 AT/AA vs TT 51 OS (ns) NA ns s15 rs1800890 TA/AA vs TT 687 PFS (ns) Newly diagnosed (34%), NA (66%) ns s9 rs6676671 AT/TT vs AA 301 FFTF (ns) NA ns s12 ABVD (59%), MOPP (9%), Stanford V (18%), BEACOPP rs6703630 n.d 149 FFTF (ns) ns s13 (11%), VEBEP (1%), Radiotherapy (2%) rs6703630 GA/AA vs GG 94 FFS (ns) NA ns s14 Genes SNP Allele comparison Patients Endpoint results Treatment Statistics HR/RR (95% CI) Comments Results References IL13 rs1800925 n.d 301 FFTF (ns) NA ns s12 Not significant rs20541 n.d 301 FFTF (ns) NA ns s12 IL1RN rs419598 TC/CC vs TT 438 PFS (ns) Newly diagnosed (34%), NA (66%) ns s9 ABVD/ChIVPP (70%), BEACOPP (11%), CHOP/COP/CHOEP IL4 rs2243248 GT/GG vs TT 220 EFS/OS (ns) ns Not significant 69 (19%) + Radiotherapy IL4R rs1801275 n.d 301 FFTF (ns) NA ns s12 rs1805010 n.d 301 FFTF (ns) NA ns s12 Not significant ABVD/ChIVPP (70%), BEACOPP (11%), CHOP/COP/CHOEP rs2107356 AG/GG vs AA 220 EFS/OS (ns) ns 69 (19%) + Radiotherapy ABVD (59%), MOPP (9%), Stanford V (18%), BEACOPP IL6 rs1800795 GC/CC vs GG 183 Adverse FFTF p=0.01 1.9 (1.15-3.28) Italy s13 (11%), VEBEP (1%), Radiotherapy (2%) Inconsistent rs1800795 GC/CC vs GG 314 OS/DSS (ns) Newly diagnosed ns Scotland+Newcastle s7 rs1800795 GC/CC vs GG 440 PFS (ns) Newly diagnosed (34%), NA (66%) ns France+ USA s9 KRT81 rs3660 n.d 139 DFS/OS (ns) ABVD (52%), MOPPABVD (38%) ns Not significant 71 MDR1 rs1045642 TT vs CC 130 CR (ns) ABVD ns Not significant 43 MIR146A rs2910164 CC vs GG 141 DFS/OS (ns) ABVD (52%), MOPPABVD (38%) ns Not significant 71 MIR149 rs2292832 TT vs CC 104 DFS/OS (ns) ABVD (52%), MOPPABVD (38%) ns Not significant 71 MIR196A2 rs11614913 TT vs CC 100 DFS/OS (ns) ABVD (52%), MOPPABVD (38%) ns Not significant 71 MIR423 rs6505162 CC vs AA 110 DFS/OS (ns) ABVD (52%), MOPPABVD (38%) ns Not significant 71 ABVD (59%), MOPP (9%), Stanford V (18%), BEACOPP TNFA rs1800629 n.d 184 FFTF (ns) ns s13 (11%), VEBEP (1%), Radiotherapy (2%) rs1800629 AG/AA vs GG 270 Adverse PFS Newly diagnosed (34%), NA (66%) p=0.002 2.52 (1.39-4.58) Associated to EBV- cHL Inconsistent s9 ABVD (59%), MOPP (9%), Stanford V (18%), BEACOPP rs1800630 n.d 184 FFTF (ns) ns s13 (11%), VEBEP (1%), Radiotherapy (2%) TP53 rs1042522 GG vs GC/CC 212 OS (ns) NA ns Not significant s8 TRBP rs784567 TT/TC vs CC 141 Adverse DFS ABVD (52%), MOPPABVD (38%) p=0.05 2.6 (0.97-12.09) Significant 71 ABVD/ChIVPP (70%), BEACOPP (11%), CHOP/COP/CHOEP UGT1A1 TA66 TA66 vs 67/77 224 Adverse OS p=0.003 4.2 (1.62-10.9) 69 (19%) + Radiotherapy Significant TA66 TA66 vs 67/77 273 Adverse FFP/OS/FFTF ABVD(66%), EBVP (22%), BEACOPP (12%) p=0.004 2.7 (1.37-5.31) 68 XPO5 rs11077 AA/CC vs AC 141 Adverse DFS ABVD (52%), MOPPABVD (38%) p=0.041 2.6 (1.03-6.62) Significant 71 Note: Shaded blue and bold Significant consistent findings in >1 study or with apropriate statistics Treatment regimens Not bold Inconsistent findings ABVD Doxorubicin, bleomycin, vinblastine, dacarbazine Italics Not significant findings BEACOPP Bleomycin,etoposide,doxorubicin,cyclophosphamide,vincristine,prednisolone,procarbazine Cases/controls with * Total number of cases/controls enrolled for the study C(H)O(E)P Cyclophosphamide, (doxorubicin), vincristine, (etoposide), prednisolone Cases/controls without * Number of cases/controls successfully genotyped ChlVPP Chlorambucil, vinblastine, prednisolone, procarbazine cHL Classical Hodgkin lymphoma EBVP Epirubicin, bleomycin, vinblastine, prednisone CI Confidence interval MOPP Mustargen, oncovin, procarbazine, prednisone CR Complete response Stanford V Doxorubicin,vinblastine,mechlorethamine,vincristine,bleomycin,etoposide, prednisone DFS Disease free survival VEBEP Etoposide, epirubicin, bleomycin, cyclophosphamide and prednisolone EFS Event free survival FFP Free from progression FFS Failure free survival FFTF Freedom from treatment failure EBV Epstein Barr virus HR Hazard ratio LD Linkage disequilibrium NA Not available n.d No data ns Not significant OS Overall survival RR Relative risk.
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