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Background <p>Polymorphisms in voltage-gated sodium channel (SCN) genes have been implicated in oxaliplatin-induced peripheral neuropathy (OXAIPN). However, their association with chronic OXAIPN in Japanese patients remains unclear. This study investigated the association between SCN gene polymorphisms and patient-reported chronic OXAIPN outcomes in Japanese patients with colorectal cancer.</p> Methods <p>Seventy-six Japanese patients with colorectal cancer who received oxaliplatin-containing adjuvant chemotherapy were included. Seven polymorphisms, namely <i>SCN4A</i> rs2302237, <i>SCN5A</i> rs11720524, <i>SCN9A</i> rs6746030 and rs6754031, <i>SCN10A</i> rs6800541 and rs12632942, and <i>GSTP1</i> rs1695, were analyzed. Chronic OXAIPN was assessed using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) score as the primary endpoint, while symptom severity assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was evaluated as a key secondary endpoint. Assessments were conducted at treatment completion (0&#xa0;M) and 6 months after treatment completion (6&#xa0;M).</p> Results <p>The mean age of the patients was 64.6 ± 9.9 years, and 50 patients (65.8%) were male. The mean cumulative oxaliplatin dose was 792 ± 184&#xa0;mg/m². In multivariate analyses, carriers of the <i>SCN4A</i> rs2302237 variant allele had lower FACT/GOG-Ntx scores than non-carriers at both 0&#xa0;M (B = − 4.385, 95% confidence interval [CI]: −7.938 to − 0.831, <i>p</i> = 0.016) and 6&#xa0;M (B = − 5.150, 95% CI: −8.975 to − 1.326, <i>p</i> = 0.009), indicating a lower patient-reported neuropathy-related symptom burden. In contrast, carriers of the <i>SCN10A</i> rs6800541 variant allele had higher FACT/GOG-Ntx scores at 0&#xa0;M (B = 4.564, 95% CI: 0.393 to 8.735, <i>p</i> = 0.032); however, no similar association was observed at 6&#xa0;M. PRO-CTCAE severity analyses showed similar trends for <i>SCN4A</i> rs2302237 and <i>SCN10A</i> rs6800541.</p> Conclusions <p>In this exploratory study of Japanese patients with colorectal cancer, <i>SCN4A</i> rs2302237 was consistently associated with a lower neuropathy-related symptom burden at both 0&#xa0;M and 6&#xa0;M. These findings suggest that <i>SCN4A</i> rs2302237 may be a candidate marker associated with patient-reported chronic OXAIPN symptom burden; however, larger validation studies are needed to confirm its clinical significance.</p>

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Association between voltage-gated sodium channel gene polymorphisms and chronic oxaliplatin-induced peripheral neuropathy in Japanese patients with colorectal cancer

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  • 发表日期：

    2026年6月19日

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  • Masato Matsuura,
  • Ayumu Nagamine,
  • Takashi Masuno,
  • Akira Tabei,
  • Teruko Nasaka,
  • Hiromi Nishiba,
  • Maho Koike,
  • Yuta Takahashi,
  • Kyoko Obayashi

摘要

Background

Polymorphisms in voltage-gated sodium channel (SCN) genes have been implicated in oxaliplatin-induced peripheral neuropathy (OXAIPN). However, their association with chronic OXAIPN in Japanese patients remains unclear. This study investigated the association between SCN gene polymorphisms and patient-reported chronic OXAIPN outcomes in Japanese patients with colorectal cancer.

Methods

Seventy-six Japanese patients with colorectal cancer who received oxaliplatin-containing adjuvant chemotherapy were included. Seven polymorphisms, namely SCN4A rs2302237, SCN5A rs11720524, SCN9A rs6746030 and rs6754031, SCN10A rs6800541 and rs12632942, and GSTP1 rs1695, were analyzed. Chronic OXAIPN was assessed using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) score as the primary endpoint, while symptom severity assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was evaluated as a key secondary endpoint. Assessments were conducted at treatment completion (0 M) and 6 months after treatment completion (6 M).

Results

The mean age of the patients was 64.6 ± 9.9 years, and 50 patients (65.8%) were male. The mean cumulative oxaliplatin dose was 792 ± 184 mg/m². In multivariate analyses, carriers of the SCN4A rs2302237 variant allele had lower FACT/GOG-Ntx scores than non-carriers at both 0 M (B = − 4.385, 95% confidence interval [CI]: −7.938 to − 0.831, p = 0.016) and 6 M (B = − 5.150, 95% CI: −8.975 to − 1.326, p = 0.009), indicating a lower patient-reported neuropathy-related symptom burden. In contrast, carriers of the SCN10A rs6800541 variant allele had higher FACT/GOG-Ntx scores at 0 M (B = 4.564, 95% CI: 0.393 to 8.735, p = 0.032); however, no similar association was observed at 6 M. PRO-CTCAE severity analyses showed similar trends for SCN4A rs2302237 and SCN10A rs6800541.

Conclusions

In this exploratory study of Japanese patients with colorectal cancer, SCN4A rs2302237 was consistently associated with a lower neuropathy-related symptom burden at both 0 M and 6 M. These findings suggest that SCN4A rs2302237 may be a candidate marker associated with patient-reported chronic OXAIPN symptom burden; however, larger validation studies are needed to confirm its clinical significance.