ABCMdb

PMID: 19349540

Innocenti F, Kroetz DL, Schuetz E, Dolan ME, Ramirez J, Relling M, Chen P, Das S, Rosner GL, Ratain MJ
Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics.
J Clin Oncol. 2009 Jun 1;27(16):2604-14. Epub 2009 Apr 6., 2009-06-01 [PubMed]

Sentences

No. Mutations Sentence Comment

110 ABCC2 p.Val417Ile % of Patients HWE Exact P (white)African American (n ϭ 11) White (n ϭ 67) Other (n ϭ 7) ABCC1 IVS9 ϩ8AϾG 35588 1.000 A/A 27.3 46.3 57.1 A/G 45.4 43.3 42.9 G/G 27.3 10.4 0 ABCC1 IVS11 -48CϾT 3765129 .092 C/C 81.8 71.6 71.4 C/T 18.2 22.4 28.6 T/T 0 6.0 0 ABCC1 1684TϾC 35605 .738 T/T 9.1 6.0 14.3 T/C 27.3 34.3 14.3 C/C 63.6 59.7 71.4 ABCC1 IVS18 -30CϾG 2074087 .464 C/C 0 6.0 14.3 C/G 36.4 29.8 14.3 G/G 63.6 64.2 71.4 ABCC1 4002GϾA 2230671 .392 G/G 63.6 47.8 71.4 G/A 36.4 46.3 14.3 A/A 0 6.0 14.3 ABCC1 IVS30 ϩ18AϾG 212088 .392 A/A 18.2 4.5 0 A/G 18.2 25.4 14.3 G/G 63.6 70.1 85.7 ABCC2 -1549AϾG 1885301 .602 A/A 27.3 16.4 14.3 A/G 27.3 43.3 28.6 G/G 45.4 40.3 57.1 ABCC2 -1019AϾG 2804402 .792 A/A 54.6 40.3 57.1 A/G 45.4 44.8 28.6 G/G 0 14.9 14.3 ABCC2 -24CϾT 717620 .678 C/C 100 65.7 85.7 C/T 0 32.8 14.3 T/T 0 1.5 0 ABCC2 1249GϾA (V417I) 2273697 .043 G/G 54.5 62.7 85.7 G/A 45.5 26.9 14.3 A/A 0 10.4 0 ABCC2 IVS26 -34TϾC 17216177 1.000 T/T 72.7 94.0 85.7 T/C 27.3 6.0 14.3 C/C 0 0 0 ABCC2 3972CϾT 3740066 .790 C/C 45.5 44.8 85.7 C/T 45.5 43.3 0 T/T 9.0 11.9 14.3 ABCB1 -129TϾC 3213619 .006 T/T 100 92.5 100 T/C 0 4.5 0 C/C 0 3.0 0 ABCB1 IVS4 -25GϾT 2235015 .700 G/G 72.7 65.7 100 G/T 27.3 29.8 0 T/T 0 4.5 0 (continued on following page) Irinotecan Pharmacogenetics www.jco.org (c) 2009 by American Society of Clinical Oncology 2609 discovered this variant during a resequencing study of the region 5Ј to the UGT1A exon 119 and hypothesized that UGT1A1*93 was a better predictor of neutropenia than UGT1A1*28.6 This variant has unknown function at the molecular level and, in our study, is associated withincreasedexposureofpatientstoSN-38.DespiteitshighLDwith the UGT1A1*28 allele, our data are consistent with the recent results of a study identifying UGT1A1*93 as the only predictor of severe hematologic toxicity in colorectal cancer patients receiving fluorouracil, leucovorin, and CPT-11.20 In addition to UGT1A1, our data suggest that ABCC transporter genes play a major role in the pharmacology of CPT-11. Login to comment 115 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCC1 p.Ala893Thr % of Patients HWE Exact P (white)African American (n ϭ 11) White (n ϭ 67) Other (n ϭ 7) ABCB1 IVS9 -44AϾG 10276036 .012 A/A 45.4 37.3 0 A/G 36.4 34.3 57.1 G/G 18.2 28.4 42.9 ABCB1 1236CϾT 1128503 .012 C/C 45.5 38.8 0 C/T 54.5 34.3 57.1 T/T 0 26.9 42.9 ABCB1 IVS13 ϩ24CϾT 2235033 .027 C/C 27.3 29.9 0 C/T 45.4 35.8 57.1 T/T 27.3 34.3 42.9 ABCB1 IVS14 ϩ38AϾG 2235013 .027 A/A 18.2 29.9 0 A/G 54.5 35.8 57.1 G/G 27.3 34.3 42.9 ABCB1 2677GϾA/T (A893T/S) 2032582 .046 G/G 40.0 36.9 40.0 G/T 60.0 36.9 60.0 T/T 0 26.2 0 ABCB1 3435CϾT 1045642 .212 C/C 36.4 28.4 57.1 C/T 54.5 41.8 42.9 T/T 9.1 29.8 0 ABCG2 34GϾA (V12M) 2231137 .113 G/G 100 92.5 28.6 G/A 0 6.0 57.1 A/A 0 1.5 14.3 ABCG2 421CϾA (Q141K) 2231142 1.000 C/A 9.1 14.9 42.9 C/C 90.9 85.1 57.1 A/A 0 0 0 SLCO1B1*1b 388AϾG (N130D) 2306283 .624 A/A 18.2 31.3 0 A/G 63.6 46.3 71.4 G/G 18.2 22.4 28.6 SLCO1B1*5 521TϾC (V174A) 4149056 1.000 T/T 81.8 65.7 57.1 T/C 18.2 31.3 42.9 C/C 0 3.0 0 NOTE. Alleles for which a * nomenclature has not yet been assigned have been reported according to their genomic position related to the ATG start site. The reference sequences used for genotyping are the following: ABCG2, NM_004827; SLCO1B1, NM_006446; ABCB1, NM_000927; ABCC1, NM_004987; and ABCC2, NM_00039. Login to comment