Journal Article

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

Ozaki, Yukinori, Yunokawa, Mayu, Shiraishi, Seiji, Hasegawa, Junko, Tamura, Nobuko, Takano, Toshimi, Shimomura, Akihiko, Shimizu, Chikako, Tanabe, Yuko, Ikeda, Kazutaka, Nishizawa, Daisuke, Yonemori, Kan, Hashimoto, Kenji, Kawabata, Hidetaka, Tamura, Kenji, Fujiwara, Yasuhiro

2020

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Aged, 80 and over / Analysis / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Biomarkers / Biomedical and Life Sciences / Biomedicine / Breast and ovarian cancer / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Cancer patients / Cancer Research / Carboplatin / Chemotherapy / Chromosomes / Cyclophosphamide - administration & dosage / Deoxyribonucleic acid / DNA / Docetaxel - administration & dosage / Dorsal root ganglia / Doxorubicin - administration & dosage / EDTA / Epirubicin - administration & dosage / Female / Fluorouracil - administration & dosage / Follow-Up Studies / Gene amplification / Gene polymorphism / Genetic aspects / Genomes / Genomics / Genotype & phenotype / Genotyping / Health Promotion and Disease Prevention / Humans / Japan - epidemiology / Medicine/Public Health / Middle Aged / Mutation / NAV1.7 Voltage-Gated Sodium Channel - genetics / Oncology / Ovarian cancer / Ovarian Neoplasms - drug therapy / Ovarian Neoplasms - genetics / Ovarian Neoplasms - pathology / Paclitaxel - administration & dosage / Pain / Patients / Peripheral Nervous System Diseases - chemically induced / Peripheral Nervous System Diseases - epidemiology / Peripheral Nervous System Diseases - genetics / Peripheral Nervous System Diseases - pathology / Peripheral neuropathy / Polymorphism, Single Nucleotide / Prognosis / Prospective Studies / Quality of life / Research Article / rs13017637 / SCN10A / SCN9A / Single nucleotide polymorphisms / Single-nucleotide polymorphism / Sodium channels (voltage-gated) / Software / Surgical Oncology / Survival Rate / Taxane-induced peripheral neuropathy