Abstract

e13656 Background: A retrospective study was carried out to investigate the association of functional rs7372209 single nucleotide polymorphism (SNP) in the 5'- region of pri-miRNA- 26a1 gene with a risk of colorectal cancer (CRC) in a Bulgarian population, to evaluate its role as a potential prognostic or predictive biomarker for the disease and to studied its affection on the expression of miRNA-26a-1 in patients with CRC. Methods: 101 patients with colorectal metastatic disease and 90 healthy volunteers, all Caucasians from Bulgaria, were genotyped for rs7372209 SNP by qPCR method. The expression levels of miRNA-26a in sera also have been determined. U6 was used as endogenous constitutively expressed control. Relative gene expression was calculated using 2−∆∆Ct method. Results: TT genotype in rs7372209 SNP was significantly overrepresented in CRC patients with right-sided colon cancer when compared with CRC patients with left-sided colon cancer, and rectal cancer (33% vs. 8%, OR = 6.13, 95% CI: 1.56–23.97, p = 0.009). Patients with TT genotype in rs7372209 SNP had significantly (p = 0.041) longer mean overall survival (OS) of 26 months (95% CI: 21.76–34.18) as compared to those with CT and CC genotypes – 19 months (95% CI: 16.43–22.20). Expression levels of miR-26a in sera were significantly higher in CRC patients compared to healthy volunteers. The ROC analysis revealed that miR-26a can effectively discriminate between CRC patients and the healthy volunteers (AUC = 0.830, 95% CI: 0.77–0.89, p < 0.001). Patients with TT genotype in rs7372209 SNP had a numeric lower mean level of miR-26a-1 – 4.702 in comparison with patients that harboring CT or CC genotype – 6.507. Conclusions: Our data suggest that high serum levels of miR-26a-1 are potentially useful as a diagnostic biomarker for CRC. Although, that patients with ТТ genotype had often more aggressive right-sided colon cancer they had longer mean overall survival than patients harboring CT or CC genotype of rs7372209.

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