Genetic Variation in MiRNA Processing Machinery Genes and Susceptibility to Colorectal Cancer in the Iranian Population

Marzieh  Mobaraki; Hamid Asadzadeh  Aghdaei; Seyed  Abdolhamid Angaji; Ehsan  Nazemalhosseini-Mojarad; Sedigheh  Arbabian

doi:10.18502/ijph.v53i12.17334

Marzieh Mobaraki Department of Biology, Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran
Hamid Asadzadeh Aghdaei Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Seyed Abdolhamid Angaji Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Hesarak, Tehran, Iran
Ehsan Nazemalhosseini-Mojarad Department of Cancer, Gastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Diseas-es, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Sedigheh Arbabian Department of Biology, Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran

DOI: https://doi.org/10.18502/ijph.v53i12.17334

Keywords: Colorectal cancer; Single-nucleotide polymorphisms; Genetics

Abstract

Background: We aimed to elucidate the potential correlation between single-nucleotide polymorphisms (SNPs) in miRNA machinery genes and colorectal cancer (CRC) risk in an Iranian cohort.

Methods: We conducted a robust case‒control study involving 507 participants, which included 213 patients diagnosed with CRC and 294 healthy controls at Research Institute for Gastroenterology and Liver Diseases in Tehran Province, Iran in 2018. The study focused on genotyping four specific SNPs, RAN (rs14035), GEMIN3 (rs197412), GEMIN4 (rs2740348), and Dicer (rs3742330), using advanced ARMS-PCR and Tetra-primer ARMS-PCR techniques.

Results: Notably, our investigation revealed the significant inverse association between the C/C genotype of rs197412 in the GEMIN3 gene and CRC risk (OR=0.54, 95% CI=0.33-0.87; P=0.0087). In stark contrast, the T/T genotype of rs14035 in the RAN gene was strongly associated with a heightened risk of developing CRC (OR=4.44, 95% CI=2.60-7.57, P<0.0001). Furthermore, we found that the G/G genotype of rs2740348 in GEMIN4 posed an increased risk for CRC (OR=2.9, 95% CI=1.44-5.85, P=0.0041) and it has a major effect on CRC risk in our population. The alleles and genotypes of rs3742330 in Dicer, however, did not exhibit a significant correlation with CRC.

Conclusion: Our study provides compelling evidence that SNPs within miRNA processing genes significantly contribute to susceptibility to CRC among the Iranian population. Our research not only contributes to the growing body of miRNA-related genetic studies but also opens avenues for population-specific risk assessment and personalized medicine approaches in cancer therapy.