ABCMdb

PMID: 17925548

Marsh S, Paul J, King CR, Gifford G, McLeod HL, Brown R
Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer: the Scottish Randomised Trial in Ovarian Cancer.
J Clin Oncol. 2007 Oct 10;25(29):4528-35., 2007-10-10 [PubMed]

Sentences

No. Mutations Sentence Comment

55 ABCG2 p.Gln141Lys ABCC2 p.Val417Ile Homozygous Wild-Type Heterozygous Homozygous Variant p‫ء‬ q† ABCB1 1236CϾT Pac, Doc 896 287 448 161 0.57 0.43 ABCB1 2677GϾT‡§ Pac, Doc 900 269 416 162 0.55 0.42 ABCB1 3435CϾT Pac, Doc 898 207 445 246 0.48 0.52 ABCC1 S1334S Pac, Doc 890 469 360 61 0.73 0.27 ABCC1 IVS18-30CϾG Pac, Doc 886 649 215 22 0.85 0.15 ABCC2 24CϾT Pac, Doc, Carb 899 593 277 29 0.81 0.19 ABCC2 IVS12ϩ148AϾG Pac, Doc, Carb 892 338 422 132 0.62 0.38 ABCC2 V417I Pac, Doc, Carb 867 575 264 28 0.82 0.18 ABCG2 Q141K Pac, Doc, Carb 904 726 168 10 0.90 0.10 CDKN1A 10971CϾT Pac, Doc 873 749 124 0 0.93 0.07 CYP1B1‫ء‬ 3 Pac, Doc 823 228 421 174 0.53 0.47 CYP2C8 M264I Pac 892 683 191 18 0.94 0.06 CYP2C8 R139K Pac 905 799 104 2 0.87 0.13 CYP2C8 K399R Pac 841 650 174 17 0.88 0.12 CYP3A4‫ء‬ 1B Pac, Doc 875 838 37 0 0.98 0.02 CYP3A4‫ء‬ 3ʈ Pac, Doc 900 893 7 0 0.996 0.004 CYP3A5‫ء‬ 3C Pac, Doc 883 6 95 782 0.06 0.94 ERCC1 17677GϾT Carb 889 742 136 11 0.91 0.09 ERCC1 8092CϾA Carb 854 477 317 60 0.74 0.26 ERCC1 N118N Carb 869 347 396 126 0.63 0.37 ERCC2 K751Q Carb 901 367 398 136 0.63 0.37 GSTP1 A114V Carb 867 748 114 5 0.93 0.07 GSTP1 I105V Carb 881 394 367 120 0.66 0.34 MAPT P587P Pac, Doc 853 791 59 3 0.96 0.04 MPO -463GϾA Carb 888 565 277 46 0.79 0.21 TP53 R72P Pac, Doc 877 495 323 59 0.75 0.25 XRCC1 R399Q Carb 869 390 395 84 0.68 0.32 Abbreviations: SCOTROC1, Scottish Randomised Trial in Ovarian Cancer; Pac, paclitaxel; Doc, docetaxel; Carb, carboplatin. Login to comment 72 ABCG2 p.Gln141Lys ABCC2 p.Val417Ile However, in a study Table 3. Uncorrected P Values From ␹2 Analysis of Development Set From SCOTROC1 Data Gene and Variant Neurotoxicity (paclitaxel) Neurotoxicity (docetaxel) Hematologic (docetaxel) Grade 3/4 GI (paclitaxel) Grade 3/4 GI (docetaxel) ABCB1 1236CϾT .790 .179 .864 .649 .559 ABCB1 2677GϾT/A .816 .783 .740 .382 .472 ABCB1 3435CϾT .362 .771 .345 .507 .919 ABCC1 S1334S .981 .745 .327 .880 .125 ABCC1 IVS18-30CϾG .943 1.000 .623 .053 .354 ABCC2 -24CϾT .975 .567 .348 .961 .537 ABCC2 IVS12ϩ148AϾG .655 .935 .227 .570 .017 ABCC2 V417I .059 .738 .351 .838 .182 ABCG2 Q141K .711 .318 .838 .086 .205 CDKN1A 10971CϾT .359 1.000 .094 .483 .002‫ء‬ CYP1B1‫ء‬ 3 .709 .587 .764 .175 .006‫ء‬ CYP2C8 M264I .601 .069 1.000 1.000 .148 CYP2C8 R139K .421 .315 .314 .020 .157 CYP2C8 K399R .232 .353 .285 .007 .147 CYP3A4‫ء‬ 1B .590 1.000 .714 .750 .743 CYP3A5‫ء‬ 3C .121 .243 1.000 .730 .272 ERCC1 17677GϾT .171 .079 .705 .159 .638 ERCC1 8092CϾA .010 .662 .069 .683 .975 ERCC1 N118N .261 .427 .171 .655 .981 ERCC2 K751Q .206 .209 .501 .062 .108 GSTP1 A114V .231 .400 .812 1.000 .072 GSTP1 I105V .205 .018 .467 .566 .277 MAPT P587P .797 .308 .590 .329 .361 MPO -463GϾA .236 .724 .829 .496 .138 TP53 R72P .298 .954 .945 .490 .157 XRCC1 R399Q .917 .467 .068 .793 .977 NOTE. Login to comment 94 ABCG2 p.Gln141Lys ABCC2 p.Val417Ile For example, polymorphisms in SLCO1B3 were not associated with taxanepharmacokinetics.42 Inadditiontoidentifyingfunctionalpoly- morphisms in known candidate genes, ongoing genome-wide strategies may provide novel candidate genes/chromosome regions for future pharmacogenetics studies.43 Recent studies also suggest that Table 4. Uncorrected P Values From ␹2 (response) and Log-Rank (progression-free survival) Analysis for Genotype-Outcome Associations in the Development Set Gene and Variant Progression-Free Survival (567-594 patients) CA-125 Response (260-287 patients) Clinical/Radiologic Response (295- 341 patients) ABCB1 1236CϾT .719 .897 .541 ABCB1 2677GϾT/A‫ء‬ .023 .308 .138 ABCB1 3435CϾT .614 .500 .740 ABCC1 S1334S .671 1.000 .903 ABCC1 IVS18-30CϾG .335 .226 .305 ABCC2 -24CϾT .619 .616 .693 ABCC2 IVS12ϩ148AϾG .712 .689 .848 ABCC2 V417I .278 .582 .503 ABCG2 Q141K .427 1.000 .344 CDKN1A 10971CϾT .305 .014 1.000 CYP1B1‫ء‬ 3 .120 .865 .291 CYP2C8 M264I .481 .762 .295 CYP2C8 R139K .572 .080 .154 CYP2C8 K399R .617 .004 .319 CYP3A4‫ء‬ 1B .687 1.000 .780 CYP3A5‫ء‬ 3C .499 .570 .909 ERCC1 17677GϾT .517 .292 .635 ERCC1 8092CϾA .677 .029 .593 ERCC1 N118N .851 .214 .204 ERCC2 K751Q .562 .613 .198 GSTP1 A114V .178 .512 .243 GSTP1 I105V .693 .187 .939 MAPT P587P .253 1.000 .827 MPO -463GϾA .537 .349 .088 TP53 R72P .212 .878 .309 XRCC1 R399Q .254 .422 .256 NOTE. Login to comment