Association of rs363293 single nucleotide polymorphism in promoter region of miRNA-143/145 with susceptibility to colorectal cancer and with patients’ outcome

Abstract

Abstract Background miRNA-143 and miRNA-145 are known as suppressors of tumor cell proliferation and migration, and in triggering of apoptosis. Both miRNAs have been shown to be down-regulated in colorectal cancer (CRC). miRNA-143 and miRNA-145 are encoded from gene cluster on chromosome 5q32 and probably originate from the same primary RNA. The aim of the present study was to determine the possible association of gene variant in promoter region of miRNA-143/145 with risk of CRC in a Bulgarian population and to evaluate the role of the rs363293 single nucleotide polymorphism (SNP) as potential prognostic and/or predictive biomarker of the disease. Methods 99 patients with CRC and 89 healthy volunteers, all Caucasians from Bulgaria, were genotyped for rs363293 SNP by qPCR method. The expression levels of miRNA-143 and miRNA-145 in sera also have been determined. Relative gene expression was calculated using 2-ΔΔCt method. Results AA genotype in rs363293 SNP was significantly overrepresented in CRC patients when compared with healthy volunteers (32% vs 19%, OR = 2.02, 95% CI: 1.03–3.98, p = 0.041). Patients with AA genotype in rs363293 SNP had significantly (p = 0.033) longer mean overall survival (OS) of 21.9 months (95% CI: 17.72–26.12) as compared to those with CT and CC genotypes – 16.6 months (95% CI: 13.72–19.51). In the multivariate analysis, AA genotype in rs363293 SNP showed a trend towards better outcome (HR = 0.59, 95% CI: 0.33–1.08, p = 0.086). The association results for genotypes in rs363293 SNP and reduced expression levels of miR-143 and/or miR-145 in sera were not significant. Conclusions Our data suggest the implication of the A allele in rs363293 SNP as a risk factor for CRC in a homozygous status for Caucasians or at least for a Bulgarian population and for patients - AA genotype has prognostic significance. Legal entity responsible for the study The authors. Funding Medical University of Varna (Grant number FMS-53/18.12.2017) and Bulgarian National Science Fund (Grant number КП-06-H23/6, 18.12.2018). Disclosure All authors have declared no conflicts of interest.