Association of rs7372209 single nucleotide polymorphism in gene for miRNA-26a-1 with tumor localization and disease outcome in patients with colorectal cancer from Bulgaria.

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.

Single Nucleotide Polymorphisms in microRNA Genes and Colorectal Cancer Risk and Prognosis

“…Another study observed worse clinical RFS of CRC patients in the II stage undergoing adjuvant chemo-radiotherapy who harbored T allele under dominant (CT + TT vs. CC) and overdominant (CT vs. CC + TT) genetic models [ 28 ]. In comparison, we found in a group of mCRC patients that TT genotype was significantly overrepresented in CRC patients with right-sided colon cancer than in patients with left-sided colon cancer and rectal cancer and associated with a longer mean OS than CT and CC genotypes [ 115 ].…”