Single nucleotide polymorphisms to predict taxanes toxicities and effectiveness in cancer patients.
ATP Binding Cassette Transporter, Subfamily B
/ genetics
Adult
Aged
Aged, 80 and over
Albumins
/ therapeutic use
Cytochrome P-450 CYP3A
/ genetics
Docetaxel
/ therapeutic use
Female
Genotype
Humans
Male
Middle Aged
Neoplasms
/ drug therapy
Paclitaxel
/ therapeutic use
Pharmacogenetics
/ methods
Polymorphism, Single Nucleotide
/ genetics
Prospective Studies
Taxoids
/ adverse effects
Journal
The pharmacogenomics journal
ISSN: 1473-1150
Titre abrégé: Pharmacogenomics J
Pays: United States
ID NLM: 101083949
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
24
07
2020
accepted:
03
02
2021
revised:
28
01
2021
pubmed:
3
3
2021
medline:
29
1
2022
entrez:
2
3
2021
Statut:
ppublish
Résumé
Taxanes are used in the treatment of several solid tumours. Adverse events (AEs) might be influenced by single nucleotide polymorphisms (SNPs) in genes encoding proteins responsible for pharmacokinetic and pharmacodynamic. In this prospective, monocentric, observational study we explored the effect of SNPs in the main genes involved in taxanes metabolism and transport, on toxicity and efficacy in 125 patients (pts) treated with paclitaxel, nab-paclitaxel, or docetaxel for neoplasms. There was no statistically significant association between the investigated SNPs and AEs. The heterozygous genotype of CYP3A4*22 showed a trend of association with skin reactions in pts treated with paclitaxel and nab-paclitaxel (RR = 6.92; 95% CI 0.47, 99.8; p = 0.0766). CYP2C8*3/*4 variant carriers showed a trend of association with overall AEs in pts treated with paclitaxel and nab-paclitaxel (RR = 1.28; 95% CI 0.96, 1.67; p = 0.0898). No statistically significant relationship with treatment efficacy was found. ABCB1 3435TT showed a trend of association with a higher treatment response (RR = 0.22; 95% CI 0.03, 1.51; p = 0.0876). Despite the population was heterogeneous, CYP3A4*22 and CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel toxicity and ABCB1 c.3435 may affect taxanes effectiveness, even if any statistically significant was found.
Identifiants
pubmed: 33649523
doi: 10.1038/s41397-021-00227-7
pii: 10.1038/s41397-021-00227-7
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
ATP Binding Cassette Transporter, Subfamily B
0
Albumins
0
Taxoids
0
Docetaxel
15H5577CQD
Cytochrome P-450 CYP3A
EC 1.14.14.1
Paclitaxel
P88XT4IS4D
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
491-497Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
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