MicroRNA (miRNA) is a class of small non-coding molecular that functions as oncogene or tumor suppressors in malignancies including colorectal cancer (CRC). Polymorphisms within miRNA can affect the processing of its maturation, expression or binding to its targeted mRNA, leading to dysfunction of miRNA and its targeted gene.
Genotypes of seven miRNA polymorphisms(miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164,miR-143/145 rs41291957, miR-124 rs531564, miR-26a-1 rs7372209 and miR-30c rs928508) were investigated in 1218 I-III stage resected CRC cases using Sequenom's MassARRAY platform.OR, HR and 95%CI were used to evaluate the strength between the loci, ORR, DCR, RFS and OS in resected CRC patients undergoing 5'-FU-based first line chemotherapy.
Rs4919510 (dominant model: adjusted OR = 0.290, 95% CI = 0.154-0.546 for ORR; co-dominant model: adjusted OR = 0.466, 95% CI = 0.257-0.847 for DCR) and rs41291957 (dominant model: adjusted OR = 0.438, 95% CI = 0.227-0.844 for ORR) were significantly associated with poor ORR and DCR, respectively. Positive associations were observed between rs2910164 (ORR: adjusted OR = 5.683,95%CI = 2.065-15.642; DCR: adjusted OR = 3.600, 95% CI = 1.193-10.861 for genotype GG vs. CC), rs531564 (DCR: adjusted OR = 2.623, 95% CI = 1.283-5.363) and response to 5'-FU-based first line chemotherapy, respectively. Moreover, rs7372209 (co-dominant model: adjusted HR = 1.195, 95% CI = 1.003-1.424) and rs531564 (dominant model: adjusted HR = 1.275, 95% CI = 1.053-1.542) were significantly associated with RFS, respectively, in resected CRC patients undergoing 5'-FU-based first line chemotherapy. However, no association was found between rs3746444, rs928508 and clinical response or survival in present study.
Our findings suggested that rs4919510 within miR-608, rs41291957 within miR-143/145, rs2910164 of miR-146A, rs531564 of miR-124 may modify clinical response to fluorouracil-based first line chemotherapy, and rs7372209 within miR-26a-1, rs531564 within miR-124 can predict a poor RFS in I-III stage CRC patients undergoing 5'-FU-based first line chemotherapy.
Clinical trial identification
Our study have no clinical trial protocol number.
All authors have declared no conflicts of interest.