Table 2.

Selected SNPs previously reported to be associated with TIPN

AuthorNumber of patientsClinical trialDrugsPhenotypeGenotypesGenes of top associationsValidation
Sucheston et al. (7)888SWOG S0221Paclitaxel (variable schedule/dose): Adjuvant-predefined number of cyclesCTC v.3.0 peripheral neuropathy—grade 0–2 (controls) vs. grade 3–4 (cases)Candidate BRCA1 and FANCD2FANCD2None
Leandro-Garcia et al. (6)214Prospective CohortPaclitaxel at variable dose ± carboplatin, gemcitabine, bevacizumab, cisplatin, cetuximab, trastuzumab, or lapatinib. Metastatic setting-variable duration.CTC v. 2.0 peripheral neuropathy—grade 2–3 (cases vs. grade 0–1 (controls)Candidate SNPs in Beta-tubulin IIaBeta-tubulin IIaNone
Hertz et al. (5)111Retrospective cohortPaclitaxel containing regimens—variable schedule and dose ± cyclophosphamide or trastuzumab. Neoaduvant-predefined duration but variableCTC v. 4.0 peripheral neuropathyCandidate metabolism SNPs: CYP1B1*3, CYP2C8*3, CYP3A4*1B/CYP3A5*3C, and ABCB1*2.CYP2C8*3None
Grade 3+ (cases)
Baldwin et al. (4)855CALGB-40101Paclitaxel 4–6 cycles: Randomized, phase III trial with planned number of cyclesCTC v. 2.0GWASFDG4European American cohort (n-154) and African American Cohort (n = 117): FDG4 significant in EA (P = 0.013) and AA subgroup; P = 6.7 × 10−3
Grade peripheral neuropathyEPHA5
Grade 2+ (cases)FZD3
Leandro-Garcia et al. (8)144Prospective cohortPaclitaxel + carboplatin: variable Metastatic: duration variable and some with prior neurotoxic chemoCTC v. 2.0GWASEPHA4No validation but EPHA5 with a significant P value in meta-analysis with CALGB40101 (4).
Grade peripheral neuropathy
Grade 2+ (cases)
Beutler et al. (9)119Alliance N08C1Paclitaxel at variable dose and schedule ± carboplatinCIPN20Targeted sequencing of 49 candidate genesARHGEF10None
Abraham et al. (10)1,303tAnGo & NeotAnGoPaclitaxel at uniform dose, but variable scheduleCTC v.2.0Genotyping 73 SNPs in 50 candidate genesABCB1GWAS pending
Apellaniz-Ruiz et al. (11)8Patients selected from hospital populationPaclitaxel at variable dose and scheduleCTC v.4.0Whole-exome sequencingCYP3A4Yes
Boso et al. (12)113Patients selected from electronic medical recordsPaclitaxel and DocetaxelCTC v.4.0Genotyping 47 SNPs in 20 candidate genesCYP3A4None
Schneider (this study)1,357 (for grade 2+ analysis)ECOG-5103Paclitaxel at uniform dose and schedule. Randomized, phase III trial with predefined number of cycles ± bevacizumabCTC v. 3.0 peripheral neuropathy. grade 2+ and grade 3+GWASSee Results sectionECOG 1199 randomized phase III trial with paclitaxel or docetaxel at variable schedule and dose.
962 for grade 3+ analysisGrade 3+ n = 488. rs3125923 P = 5.9 × 10−3