Taxane-induced sensory peripheral neuropathy is associated with an SCN9A single nucleotide polymorphism in Japanese patients.

Abstract

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:

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:

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:

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.

• Authors: Yuko Tanabe, Seiji Shiraishi, Kenji Hashimoto, Kazutaka Ikeda, Daisuke Nishizawa, Junko Hasegawa, Akihiko Shimomura, Yukinori Ozaki, Nobuko Tamura, Mayu Yunokawa, Kan Yonemori, Toshimi Takano, Hidetaka Kawabata, Kenji Tamura, Yasuhiro Fujiwara, Chikako Shimizu
• Journal: BMC cancer (BMC Cancer) Vol. 20 Issue 1 Pg. 325 (Apr 16 2020) ISSN: 1471-2407 [Electronic] England
• PMID: 32295642 (Publication Type: Journal Article)

Chemical References

• NAV1.7 Voltage-Gated Sodium Channel
• SCN9A protein, human
• Docetaxel
• Epirubicin
• Doxorubicin
• Cyclophosphamide
• Paclitaxel
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (drug therapy, genetics, pathology)
• 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, genetics, pathology)
• Paclitaxel (administration & dosage)
• Peripheral Nervous System Diseases (chemically induced, epidemiology, genetics, pathology)
• Polymorphism, Single Nucleotide
• Prognosis
• Prospective Studies
• Survival Rate