Association of microRNA SNP variants and microRNASNP-SNP interactions with colorectal cancer risk in Yemen: a case-control study

Several studies suggest that microRNA(miRNA) single-nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC). However, there is very limited data on the association between miRNA SNP-SNP interactions and CRC. This study aimed to evaluate the association between miRNA SNPs, SNP-SNP interactions, and CRC risk in a Yemeni population. This study aimed to evaluate the associations of miRNA SNPs and SNP-SNP interactions with CRC risk in a Yemeni population. A case-control study was conducted in 200 patients with CRC and 200 normal participants. Genotyping of selected miRNA SNPs, miR-146a (rs2910164), miR-27a (rs895819 ) , miR-196a-2 (rs11614913), and miR-499a (rs3746444) was performed on real-time polymerase chain reaction (RT-PCR) using TaqMan allelic discrimination assays. Logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between SNPs and CRC risk. After Bonferroni correction, the analysis revealed significant associations of miR-146a and miR-499a SNPs with CRC. Both recessive (OR = 2.1, 1.7; P = 0.0005, 0.016) and additive models (OR = 1.6, 1.3; P = 0.008, 0.037) of these SNPs showed significant associations with CRC. In contrast, SNPs in miR-27a and miR-196a-2 showed no significant association with CRC. After Bonferroni correction, the interaction between the risk genotypes, miR-146a CC and miR-499a GG, remains significantly associated with CRC risk (OR = 8.97, p = 0.01) compared with the reference group, which had both protective genotypes, miR-146a GG and miR-499a AA. The miR-146a and miR-499a polymorphisms, as well as their interaction, were associated with an increased risk of CRC in a Yemeni population. This study provides preliminary evidence for the role of miRNA SNP-SNP interactions in CRC susceptibility.