Genetic Predictors of Lung Cancer Risk: A Molecular Approach Involving microRNA Signatures

Abstract

Lung cancer is a leading cause of cancer-related deaths worldwide, with both environmental and genetic factors contributing to its development. Among genetic determinants, microRNA (miRNA) dysregulation has emerged as a critical mechanism in tumorigenesis. MiR-146a plays a pivotal role in modulating immune and inflammatory responses, and its rs2910164 polymorphism (G>C) has been implicated in cancer susceptibility. This study aimed to investigate the association between the miR-146a rs2910164 polymorphism and lung cancer risk in an Iraqi population. A case-control design was employed, involving 72 patients with histopathologically confirmed lung cancer and 70 age- and gender-matched healthy controls. Genomic DNA was extracted from peripheral blood samples, and the rs2910164 polymorphism was genotyped using Tetra-ARMS PCR. Genotypes were determined by analyzing distinct band patterns on 2% agarose gels. Statistical analyses were performed to compare genotypic and allelic frequencies between cases and controls, calculating odds ratios (OR) with 95% confidence intervals (CI) and p-values. The GC genotype showed a significantly higher frequency among lung cancer cases compared to controls (OR = 2.22, 95% CI: 1.19–4.14; p = 0.004), suggesting a potential risk factor. The C allele also demonstrated a notable association with increased lung cancer susceptibility (OR = 1.79, 95% CI: 1.11–2.89; p = 0.017). In contrast, neither the GG genotype nor the G allele exhibited a significant relationship with disease risk (p > 0.05). Collectively, our findings confirm that carriers of the miR-146a rs2910164 C allele, especially the GC carriers, are at a heightened risk of developing lung cancer in the Iraqi population. To confirm such a finding and elucidate the molecular circuitry of Iraqi carcinogenesis, however, future investigations must be extended: larger, multiethnic cohorts with control for other genetic markers, lifestyle factors, and environmental factors will be required.