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Table 1 Overview of the 26 genotyped single nucleotide polymorphisms (SNPs)

From: Genetic variability in drug transport, metabolism or DNA repair affecting toxicity of chemotherapy in ovarian cancer

Gene Name Function of the gene product Variant allele (rs number, nucleotide, amino acid change) Effect of the polymorphism on the toxicity or clinical outcome
ABCB1 Multidrug resistance 1, P-glycoprotein ATP binding membrane transporter implicated in efflux of cytotoxic agents rs1128503, c.1236C>T, Gly412Gly Homozygous carriers of the variant allele: docetaxel clearance decreased [9].
rs1045642, c.3435C>T, Ile1145Ile Variant allele carriers: more pronounced neutrophil depression following treatment with paclitaxel ± carboplatin [18] and increased AUC of the paclitaxel metabolite 3′-p-hydroxypaclitaxel [8].
Homozygous carriers of the variant allele: decreased risk of neutropenia and neurotoxicity [11]
No correlation was found with pharmacokinetics, toxicity or outcome in OC patients in different other studies [9,10,12,13,15,17].
    rs2229109,c.1199G>A, Ser400Asn Variant allele carriers: correlation with in vitro resistance to paclitaxel [22].
ABCC1 Multidrug resistance-associated protein 1 ATP binding membrane transporter implicated in efflux of cytotoxic drugs rs2230671, c.4002G>A, Ser1334Ser In vitro evidence: over-expression of ABCC1 protein has been associated with a low degree of resistance to paclitaxel [23].
rs2074087, c.2284-30G>C No correlation of variants in rs2230671 and rs2074087 with toxicity and outcome after platinum/taxane treatment in OC patients [12].
ABCC2 Multidrug resistance-associated protein 2 ATP binding membrane transporter implicated in efflux of cytotoxic drugs rs2073337, c.1668+148A>G In vitro evidence: paclitaxel and docetaxel are ABCC2 substrates in cell lines [24]. No correlation was found with toxicity or treatment outcome with platinum-taxane treatment in OC patients [12,17].
rs12762549, g.101620771C>G Variant allele carriers from Japan: increased risk for severe neutropenia following treatment with docetaxel [19].
ABCG2 ATP-binding cassette sub-family G member 2 ATP binding membrane transporter implicated in efflux of cytotoxic drugs rs2231142, c.421C>A, Gln141Lys Variant allele carriers in OC: 6-month longer median PFS following platinum/taxane-based chemotherapy [17].
ABCA1 ATP-binding cassette sub-family A member 1 ATP binding membrane transporter, efflux pump for S1P and cholesterol rs363717, c.*1896 A>G Variant allele carriers: decreased risk on thalidomide related neuropathy grade ≥2 [36].
SCLO1B3 Solute carrier organic anion transporter family member 1B3 Hepatocyte membrane transporter involved in the transport of cytotoxic drugs rs4149117, 334T>G, Ser112Ala Docetaxel and paclitaxel transport by SCLO1B3-expressing oocytes was higher compared to controls in vitro [20].
rs11045585, c.1683-5676A>G Variant allele carriers from Japan: increased docetaxel induced leukopenia/neutropenia [19], higher docetaxel clearance and lower AUC in nasopharyngeal carcinoma patients [21].
CYP1B1 Cytochrome P450 family 1, subfamily B, polypeptide 1 Enzyme in the oxidative metabolic pathway of exogenous chemicals including taxanes and estrogens rs1056836, 4326C>G, Val432Leu (CYP1B1*3) Homozygous carriers of the wild-type allele: decreased risk of grade 3/4 gastro-intestinal toxicity in docetaxel treated OC patients in the development but not in the validation set [12].
CYP3A4 Cytochrome P450, family 3, subfamily A, polypeptide 4 Enzyme in the oxidative metabolic pathway of exogenous chemicals including taxanes and estrogens rs2740574, g.135607G>A (CYP3A4*1B) CYP3A4 activity determined the dominant metabolic pathway for paclitaxel [14].
Homozygous carriers of the variant allele: decreased clearance of docetaxel [26].
Homozygous carriers of the variant allele: increased risk of invasive OC [27].
rs4986910, c.1331T>C, Met444Thr (CYP3A4*3) No correlation with pharmacokinetics, toxicity or outcome in OC patients treated with carboplatin + paclitaxel or docetaxel [9,10,12].
CYP3A5 Cytochrome P450, family 3, subfamily A, polypeptide 5 Enzyme in the oxidative metabolic pathway of exogenous chemicals including taxanes and estrogens rs776746, c.219-237G>A Homozygous carriers of the variant allele: increased neurotoxicity following paclitaxel treatment 25. No correlation with pharmacokinetics, toxicity or outcome in OC patients treated with carboplatin + paclitaxel or docetaxel [9,10,12].
TP53 Tumor protein 53 Transcription factor regulating multiple cellular functions, critical for maintenance of genomic stability rs1042522, c.215C>G, Pro72Arg Associated with a small increase in risk of OC [29], twofold increased risk of OC in proline carriers and a longer progression-free survival in homozygous arginine allele carriers [28]. Homozygous carriers of the variant allele: increased severity of neutropenia [32].
MAPT Microtubule-associated protein tau Protein stimulating tubulin polymerization, stabilizing microtubules rs11568305, c.215C>G, Pro587= No correlation with toxicity or outcome in OC patients treated with carboplatin + paclitaxel or docetaxel [12].
GSTP1 Gluthathione S-transferase pi Xenobiotic enzyme involved in the prevention of platinum-based DNA damage rs1695, c.313A>G, Ile105Val Variant allele carriers: decreased oxaliplatin-related neuropathy [30], decreased docetaxel-induced grade 2 neuropathy [31], decreased risk of hematologic toxicity [15].
rs1138272, c.341 C>T, Ala114Val Variant allele carriers compared to homozygous carriers of the wild-type allele: decreased PFS following cisplatin-gemcitabine [32].
In other studies, no association with toxicity in OC patients [12,32].
ERCC1 Excision repair cross complementation group1 Enzyme involved in nucleotide excision repair of DNA rs11615, c.354T>C, Asn118Asn Variant allele carriers: decreased platinum resistance [34].
rs3212961, 17677G>T Variant allele carriers compared to homozygous carriers of the wild-type allele: increased risk on severe neutropenia and increased likelihood of overall survival following cisplatin-gemcitabine [32].
No correlation for both genetic variants with toxicity/outcome for OC patients [12].
ERCC2 Excision repair cross complementation group2 Enzyme involved in nucleotide excision repair of DNA rs1799793, c.934G>A, Asp312Asn Variant allele carriers: increased severity of neutropenia in OC patients receiving cisplatin-cyclophosphamide [33].
SLC12A6 Solute carrier family 12 member 6 Integral membrane protein that lowers intracellular chloride concentrations rs7164902,g.34551082G>A, Leu144Leu Variant allele carriers: decreased risk on thalidomide related neuropathy grade ≥2 [36].
SERPINB2 Serpin peptidase inhibitor B member 2 Inhibitor of urokinase plasminogen activator, mediating neuro-inflammation rs6104, 1238C>G, Ser413Cys Variant allele carriers: decreased risk on thalidomide related neuropathy grade ≥2 [36].
PPARD Peroxisome proliferator-activated receptor delta Nuclear receptor protein playing a role in neuro-inflammation rs2076169, T>C Variant allele carriers: decreased risk on thalidomide related neuropathy grade ≥2 [36].
ICAM1 Intercellular Adhesion Molecule 1 Cell surface glycoprotein in endothelial and immune system cells rs1799969, 241G>A Variant allele carriers: decreased risk on thalidomide related neuropathy grade ≥2 [36].
  1. The following 7 genetic variants failed genotyping: rs2032582 (Ser893Ala in ABCB1), rs2273697 (Val417Ile in ABCC2), rs1058930 (Ile194Met in CYP2C8), rs11572080 (Arg69Lyes in CYP2C8), rs10509681 (Lys329Arg in CYP2C8), rs12721627 (Thr185Ser in CYP3A4), rs25487 (Gln398Arg in XRCC1). Rs6103 was replaced by rs6104 because these were in full linkage disequilibrium (r2 = 1.0). OC: ovarian cancer, NSCLS: non-small-cell lung carcinoma.