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ABCB1
|
Multidrug resistance 1, P-glycoprotein
|
ATP binding membrane transporter implicated in efflux of cytotoxic agents
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rs1128503, c.1236C>T, Gly412Gly
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Homozygous carriers of the variant allele: docetaxel clearance decreased [9].
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rs1045642, c.3435C>T, Ile1145Ile
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Variant allele carriers: more pronounced neutrophil depression following treatment with paclitaxel ± carboplatin [18] and increased AUC of the paclitaxel metabolite 3′-p-hydroxypaclitaxel [8].
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Homozygous carriers of the variant allele: decreased risk of neutropenia and neurotoxicity [11]
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No correlation was found with pharmacokinetics, toxicity or outcome in OC patients in different other studies [9,10,12,13,15,17].
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rs2229109,c.1199G>A, Ser400Asn
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Variant allele carriers: correlation with in vitro resistance to paclitaxel [22].
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ABCC1
|
Multidrug resistance-associated protein 1
|
ATP binding membrane transporter implicated in efflux of cytotoxic drugs
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rs2230671, c.4002G>A, Ser1334Ser
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In vitro evidence: over-expression of ABCC1 protein has been associated with a low degree of resistance to paclitaxel [23].
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rs2074087, c.2284-30G>C
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No correlation of variants in rs2230671 and rs2074087 with toxicity and outcome after platinum/taxane treatment in OC patients [12].
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ABCC2
|
Multidrug resistance-associated protein 2
|
ATP binding membrane transporter implicated in efflux of cytotoxic drugs
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rs2073337, c.1668+148A>G
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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].
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rs12762549, g.101620771C>G
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Variant allele carriers from Japan: increased risk for severe neutropenia following treatment with docetaxel [19].
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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].
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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].
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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].
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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].
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|
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].
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|
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].
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|
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].
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