Abstract
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(2) = 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(9)/L, Xelox (OR = 0.169, 95% CI: 0.054∼0.531) and >4 × 10(9)/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 (p = 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.