<title>Abstract</title><sec>
<title>Background</title>
Sodium channels located in the dorsal root ganglion, particularly Nav1.7 and Nav1.8, encoded by <italic>SCN9A</italic> and <italic>SCN10A</italic>, respectively, act as molecular gatekeepers for pain detection. Our aim was to determine the association between TIPN and <italic>SCN9A</italic> and <italic>SCN10A</italic> polymorphisms<italic>.</italic>


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<title>Methods</title>
Three single nucleotide polymorphisms (SNPs) in <italic>SCN9A</italic> and two in <italic>SCN10A</italic> 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 (<italic>N</italic> = 108) and controls (<italic>N</italic> = 78) with grade 0–1 neuropathy. Multiple logistic regression analyses were conducted to evaluate associations between TIPN and SNP genotypes.


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<title>Results</title>
<italic>SCN9A-</italic>rs13017637 was a significant predictor of grade 2 or higher TIPN (odds ratio (OR) = 3.463; <italic>P</italic> = 0.0050) after correction for multiple comparisons, and precision was improved when only breast cancer patients were included (OR 5.053, <italic>P</italic> = 0.0029). Moreover, rs13017637 was a significant predictor of grade 2 or higher TIPN 1 year after treatment (OR 3.906, <italic>P</italic> = 0.037), indicating its contribution to TIPN duration.


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<title>Conclusion</title>
<italic>SCN9A</italic> 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.


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