Abstract
Abstract
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.