RUNX1基因启动子rs2071029多态性对结直肠癌辅助化疗所致中性粒细胞减少的易感性
Susceptibility of RUNX1 promoter rs2071029 polymorphism to adjuvant chemotherapy-induced neutropenia in CRC.
作者信息
Luo Xikai, Wang Hao, Huang Zhe, Lin Zhuocheng, Li Chunpeng, Wang Qiwen, Wei Yisheng
机构信息
Department of Anorectal Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Department of Gastrointestinal Surgery, Lab of Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
出版信息
Biomark Med. 2025 Jun;19(12):471-479. doi: 10.1080/17520363.2025.2516996. Epub 2025 Jun 10.
AIM
To investigate the susceptibility of Runt-related transcription factor 1 (RUNX1) promoter polymorphism to adjuvant chemotherapy-induced neutropenia (CIN) of colorectal cancer (CRC).
METHODS
RUNX1 promoter polymorphisms rs2071029 and rs12626613 were genotyped by SnaPshot genotyping and Sanger sequencing. The association of rs2071029 and CIN in 204 CRC patients was analyzed using chi-square test and multivariate logistic regression model. The impact of rs2071029 polymorphism on RUNX1 promoter activity was analyzed by luciferase assay.
RESULTS
Rs2071029 and rs12626613 loci were in strong linkage disequilibrium (D ' = 0.957. r = 0.878). Compared with rs2071029 CC genotype, TT (OR = 0.250, 95% CI: 0.101∼0.617) had a decreased risk of severe CIN. Compared with mFOLFOX6,and baseline neutrophil counts 2-4 × 10/L, Xelox (OR = 0.169, 95% CI: 0.054∼0.531) and >4 × 10/L(OR = 0.446 95% CI: 0.209∼0.952) had a decreased risk of severe CIN, respectively. Rs2071029T promoter activity was significantly higher than that of rs2071029C promoter ( = 0.014). Stratified analyses revealed that the protective effect of the rs2071029 TT was more pronounced in patients over 60 years (OR = 0.139, 95% CI: 0.031-0.622) and stage II cases (OR = 0.117, 95% CI: 0.018-0.745).
CONCLUSION
RUNX1 promoter rs2071029 polymorphism could be useful as an independent biomarker for CIN in CRC.
目的
探讨 runt 相关转录因子 1（RUNX1）启动子多态性对结直肠癌（CRC）辅助化疗引起的中性粒细胞减少症（CIN）的易感性。
方法
采用 SnaPshot 基因分型和 Sanger 测序对 RUNX1 启动子多态性 rs2071029 和 rs12626613 进行基因分型。采用卡方检验和多因素逻辑回归模型分析 204 例 CRC 患者中 rs2071029 与 CIN 的相关性。通过荧光素酶报告基因检测分析 rs2071029 多态性对 RUNX1 启动子活性的影响。
结果
rs2071029 和 rs12626613 位点处于强连锁不平衡状态（D' = 0.957，r = 0.878）。与 rs2071029 CC 基因型相比，TT 基因型（OR = 0.250，95%CI：0.101～0.617）发生严重 CIN 的风险降低。与 mFOLFOX6 方案相比，Xelox 方案（OR = 0.169，95%CI：0.054～0.531）且基线中性粒细胞计数为 2 - 4×10⁹/L，以及基线中性粒细胞计数＞4×10⁹/L（OR = 0.446，95%CI：0.209～0.952）时发生严重 CIN 的风险分别降低。rs2071029T 启动子活性显著高于 rs2071029C 启动子（P = 0.014）。分层分析显示，rs2071029 TT 基因型的保护作用在 60 岁以上患者（OR = 0.139，95%CI：0.031 - 0.622）和Ⅱ期病例（OR = 0.117，95%CI：0.018 - 0.745）中更为明显。
结论
RUNX1 启动子 rs2071029 多态性可作为 CRC 中 CIN 的独立生物标志物。
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