Taxane-induced sensory peripheral neuropathy is associated with an SCN9A single nucleotide polymorphism in Japanese patients.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Breast Neoplasms
/ drug therapy
Cyclophosphamide
/ administration & dosage
Docetaxel
/ administration & dosage
Doxorubicin
/ administration & dosage
Epirubicin
/ administration & dosage
Female
Fluorouracil
/ administration & dosage
Follow-Up Studies
Humans
Japan
/ epidemiology
Middle Aged
NAV1.7 Voltage-Gated Sodium Channel
/ genetics
Ovarian Neoplasms
/ drug therapy
Paclitaxel
/ administration & dosage
Peripheral Nervous System Diseases
/ chemically induced
Polymorphism, Single Nucleotide
Prognosis
Prospective Studies
Survival Rate
Breast and ovarian cancer
SCN10A
SCN9A
Taxane-induced peripheral neuropathy
rs13017637
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
16 Apr 2020
16 Apr 2020
Historique:
received:
27
11
2019
accepted:
06
04
2020
entrez:
17
4
2020
pubmed:
17
4
2020
medline:
12
1
2021
Statut:
epublish
Résumé
Sodium channels located in the dorsal root ganglion, particularly Nav1.7 and Nav1.8, encoded by SCN9A and SCN10A, respectively, act as molecular gatekeepers for pain detection. Our aim was to determine the association between TIPN and SCN9A and SCN10A polymorphisms. Three single nucleotide polymorphisms (SNPs) in SCN9A and two in SCN10A were investigated using whole-genome genotyping data from 186 Japanese breast or ovarian cancer patients classified into two groups as follows: cases that developed taxane-induced grade 2-3 neuropathy (N = 108) and controls (N = 78) with grade 0-1 neuropathy. Multiple logistic regression analyses were conducted to evaluate associations between TIPN and SNP genotypes. SCN9A-rs13017637 was a significant predictor of grade 2 or higher TIPN (odds ratio (OR) = 3.463; P = 0.0050) after correction for multiple comparisons, and precision was improved when only breast cancer patients were included (OR 5.053, P = 0.0029). Moreover, rs13017637 was a significant predictor of grade 2 or higher TIPN 1 year after treatment (OR 3.906, P = 0.037), indicating its contribution to TIPN duration. SCN9A rs13017637 was associated with the severity and duration of TIPN. These findings are highly exploratory and require replication and validation prior to any consideration of clinical use.
Sections du résumé
BACKGROUND
BACKGROUND
Sodium channels located in the dorsal root ganglion, particularly Nav1.7 and Nav1.8, encoded by SCN9A and SCN10A, respectively, act as molecular gatekeepers for pain detection. Our aim was to determine the association between TIPN and SCN9A and SCN10A polymorphisms.
METHODS
METHODS
Three single nucleotide polymorphisms (SNPs) in SCN9A and two in SCN10A were investigated using whole-genome genotyping data from 186 Japanese breast or ovarian cancer patients classified into two groups as follows: cases that developed taxane-induced grade 2-3 neuropathy (N = 108) and controls (N = 78) with grade 0-1 neuropathy. Multiple logistic regression analyses were conducted to evaluate associations between TIPN and SNP genotypes.
RESULTS
RESULTS
SCN9A-rs13017637 was a significant predictor of grade 2 or higher TIPN (odds ratio (OR) = 3.463; P = 0.0050) after correction for multiple comparisons, and precision was improved when only breast cancer patients were included (OR 5.053, P = 0.0029). Moreover, rs13017637 was a significant predictor of grade 2 or higher TIPN 1 year after treatment (OR 3.906, P = 0.037), indicating its contribution to TIPN duration.
CONCLUSION
CONCLUSIONS
SCN9A rs13017637 was associated with the severity and duration of TIPN. These findings are highly exploratory and require replication and validation prior to any consideration of clinical use.
Identifiants
pubmed: 32295642
doi: 10.1186/s12885-020-06834-0
pii: 10.1186/s12885-020-06834-0
pmc: PMC7161266
doi:
Substances chimiques
NAV1.7 Voltage-Gated Sodium Channel
0
SCN9A protein, human
0
Docetaxel
15H5577CQD
Epirubicin
3Z8479ZZ5X
Doxorubicin
80168379AG
Cyclophosphamide
8N3DW7272P
Paclitaxel
P88XT4IS4D
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
325Subventions
Organisme : Scientific Research Grant from the Ministry of Health, Labor, and Welfare
ID : H21- 021
Organisme : National Cancer Center Research and Development Fund
ID : 23-A-30, 26-A-20
Organisme : Okinaka Memorial Institute for Medical Disease
ID : No. 2018-23
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