实用医学杂志 ›› 2026, Vol. 42 ›› Issue (17): 3188-3196.doi: 10.3969/j.issn.1006-5725.2026.17.018

• 论著·机制与实践 • 上一篇    下一篇

SCN10A、GSTP1、MTHFR基因多态性与结直肠癌患者奥沙利铂化疗致神经毒性的关系

鲁婷1, 宋海斌1, 邱会1, 宋丽良1, 关江锋2, 李磊3()   

  1. 1. 武汉市第一医院肿瘤科 (湖北 武汉 430022 )
    2. 武汉市肛肠医院中医科 (湖北 武汉 430010 )
    3. 武汉科技大学附属武汉亚心总医院肿瘤科 (湖北 武汉 430056 )
  • 收稿日期:2026-04-22 出版日期:2026-09-10 发布日期:2026-10-10
  • 通讯作者: 李磊
  • 基金资助:
    湖北省医学科研项目(2023AFC052)

Study on relationships between SCN10A, GSTP1 and MTHFR gene polymorphisms and oxaliplatin-induced peripheral neurotoxicity in patients with colorectal cancer

Ting Lu1, Haibin Song1, Hui Qiu1, Liliang Song1, Jiangfeng Guan2, Lei Li3()   

  1. 1. Department of Oncology,Wuhan No. 1 Hospital,Wuhan 430022,Hubei,China
    2. Department of Traditional Chinese Medicine,Wuhan Anorectal Hospital,Wuhan 430010,Hubei,China
    3. Department of Oncology,Wuhan Asian Heart General Hospital,Affiliated to Wuhan University of Science and Technology,Wuhan 430056,Hubei,China
  • Received:2026-04-22 Online:2026-09-10 Published:2026-10-10
  • Contact: Lei Li
  • About author:

    Lu Ting carried out the project design, data analysis and article writing. Song Haibin, Qiu Hui and Song Liliang participated in the data collection and revision. Guan Jiangfeng was responsible for the final revision of the paper. Li Lei participated in the revision and finalization of the paper. All authors read and approved the final manuscript as submitted.

摘要:

目的 探究SCN10A、谷胱甘肽S-转移酶P-1(GSTP1)、亚甲基四氢叶酸还原酶(MTHFR)基因多态性与接受奥沙利铂化疗的结直肠癌患者发生化疗所致神经毒性(OIPN)的相关性。 方法 回顾性分析2023年1月至2025年1月160例于武汉市第一医院接受含奥沙利铂方案化疗的结直肠癌患者的临床资料,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测SCN10A(rs12632942)、GSTP1 rs1695(Ile105Val)、MTHFR rs1801133(C677T)位点的基因型,分析各基因型与临床病理特征、OIPN分级和风险的关系。 结果 160例患者中,奥沙利铂所致OIPN总发生率为77.5%(124/160),其中≥ 3度重度神经毒性发生率为23.1%(37/160)。SCN10A rs12632942、GSTP1 rs1695、MTHFR rs1801133各基因型患者病理生理因素比较,差异均无统计学意义(P > 0.05);SCN10A rs12632942位点中,CT或TT基因型患者慢性OIPN发生率高于CC基因型(P < 0.05),CT或TT基因型是慢性OIPN的独立危险因素(P < 0.05);GSTP1 rs1695位点中,AG或GG基因型患者急性OIPN发生率高于AA基因型(P < 0.05),多因素分析显示AG或GG基因型是急性OIPN的独立危险因素(P < 0.05);MTHFR rs1801133各基因型间急、慢性OIPN发生率差异均无统计学意义(P > 0.05)。 结论 SCN10A rs12632942和GSTP1 rs1695基因多态性分别是结直肠癌患者慢性、急性OIPN的潜在遗传影响因素。MTHFR rs1801133与OIPN发生无显著相关性。

关键词: 结直肠癌, 奥沙利铂, 化疗所致神经毒性, SCN10A, 谷胱甘肽S-转移酶P-1, 亚甲基四氢叶酸还原酶, 基因多态性

Abstract:

Objective This study aims to investigate the correlations between SCN10A, glutathione S‑transferase P‑1 (GSTP1), and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and oxaliplatin‑induced peripheral neurotoxicity (OIPN) among colorectal cancer patients treated with oxaliplatin‑based chemotherapy. Methods The clinical data of 160 patients with colorectal cancer who received oxaliplatin-based chemotherapy at Wuhan No.1 Hospital between January 2023 and January 2025 were retrospectively analyzed. Genotypes of the SCN10A (rs12632942), GSTP1 rs1695 (Ile105Val), and MTHFR rs1801133 (C677T) loci were detected via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Associations between the genotypes of these loci, patients' clinicopathological characteristics, OIPN grading, and OIPN risk were further investigated. Results Among the 160 enrolled patients, the overall incidence of OIPN was 77.5% (124/160), and the incidence of severe neurotoxicity (grade ≥ 3) was 23.1% (37/160). Comparisons of pathophysiological characteristics across different genotype groups at the SCN10A rs12632942, GSTP1 rs1695, and MTHFR rs1801133 loci revealed no statistically significant between-group differences (all P > 0.05). At the SCN10A rs12632942 locus, patients with the CT or TT genotype had a significantly higher incidence of chronic OIPN than patients with the CC genotype (P < 0.05), and the CT or TT genotype was identified as an independent risk factor for chronic OIPN (P < 0.05). At the GSTP1 rs1695 locus, patients with the AG or GG genotype had a significantly higher incidence of acute OIPN than patients with the AA genotype (P < 0.05). Multivariate regression analysis confirmed that the AG or GG genotype is an independent risk factor for acute OIPN (P < 0.05). No statistically significant differences in the incidence of either acute or chronic OIPN were observed across different genotype groups at the MTHFR rs1801133 locus (all P > 0.05). Conclusions SCN10A rs12632942 and GSTP1 rs1695 polymorphisms are potential genetic risk factors for chronic and acute OIPN in patients with colorectal cancer, respectively. No significant correlation was observed between MTHFR rs1801133 and the occurrence of OIPN.

Key words: colorectal cancer, oxaliplatin, chemotherapy-induced neurotoxicity, SCN10A, glutathione S-transferase P-1, methylenetetrahydrofolate reductase, gene polymorphism

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