Carriers of the SCN4A rs2302237 variant allele had significantly lower FACT/GOG-Ntx scores at treatment completion (B = -4.385) and 6 months later, indicating a lower oxaliplatin-induced peripheral neuropathy symptom burden.
Observational (n=76)
Yes
Do SCN gene polymorphisms affect the severity of chronic oxaliplatin-induced peripheral neuropathy in Japanese patients with colorectal cancer?
The SCN4A rs2302237 polymorphism is associated with a lower patient-reported chronic oxaliplatin-induced peripheral neuropathy symptom burden in Japanese patients with colorectal cancer.
Mean Difference: -4.385 (95% CI -7.938–-0.831)
p-value: p=0.016
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.
Matsuura et al. (Fri,) conducted a observational in Colorectal cancer (n=76). SCN4A rs2302237 variant allele vs. Non-carriers of SCN4A rs2302237 variant allele was evaluated on FACT/GOG-Ntx score at treatment completion (0M) (B = -4.385, 95% CI -7.938 to -0.831, p=0.016). Carriers of the SCN4A rs2302237 variant allele had significantly lower FACT/GOG-Ntx scores at treatment completion (B = -4.385) and 6 months later, indicating a lower oxaliplatin-induced peripheral neuropathy symptom burden.