miR-146a and miR-196a2 as Novel Biomarkers for Colorectal Cancer

Background: Colorectal cancer (CRC) is among the most prevalent malignancies globally, showing increased incidence in Iraq recently, and is a malignancy that arises from the colon or rectum, which are parts of the large intestine involved in the final stages of digestion. CRC ranks as the third most common cancer worldwide and the second most common locally. The objective is to investigate the association between gene polymorphisms of miRNA-146a and miRNA-196a2, specifically the single-nucleotide polymorphisms miR-146a (rs2910164 C/G) and miR-196a2 (rs11614913 C/T), and their expression levels in CRC patients. Methodology: This case-control study evaluated genetic variation and expression levels of miR146a and miR-196a2 in CRC. Blood samples were collected from 60 clinically confirmed CRC patients and 60 healthy controls at Najaf Alsharaf National Hospital for Oncology and Haematology Centre, Iraq, from January 2024 to February 2025. RNA extracted from blood was used to measure gene expression by RT-qPCR, while DNA analysis (T-ARMS-PCR) assessed allele distribution and SNP genotype of the miR146a and miR-196a2 genes. Results: The comparison of miRNA 146a genotyping showed three genotypes: CC, CG, and GG, with frequencies of 18.2%, 73.3%, and 81.5%, respectively, in CRC patients, compared to 81.8%, 18.5%, and 26.3% in healthy individuals. The GG genotype was more frequent in patients, whereas CC was predominantly found in healthy subjects. Similarly, miRNA 196a2 genotyping identified three genotypes: CC, CT, and TT, with distributions of 23.6%, 67.7%, and 76.5% in CRC patients and 76.4%, 23.5%, and 32.3% in healthy subjects. The TT genotype was prevalent among patients, while the CC genotype was more common in healthy individuals. Conclusion: This study indicates that neither genotypes nor alleles can be considered risk or protective factors for disease development. Additionally, miR-146a (rs2910164 C/G), CG genotype, GG genotype, CT genotype, and TT genotype, as well as miR-196a2, are noted. The Etiologic Fraction (EF) measures the portion of disease incidence attributable to a specific risk factor. The SNP in the miR-196a2 gene has been widely researched for its potential role in colorectal cancer susceptibility.