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

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].