Genetic Determinants of Radiosensitivity: Evidence of Radioresistance-Associated SNP Enrichment in Occupational Workers Chronically Exposed to Low-Dose Radiation

<b>Background</b>: Interindividual radiosensitivity is largely driven by genetic regulation of DNA damage recognition, repair, and cell-cycle control. <i>TP53</i> and <i>CDKN1A</i> (<i>p21</i>) are key genomic markers associated with differential responses to ionizing radiation. <b>Methods</b>: This study investigated eight functional SNP markers across several key genes involved in DNA damage responses and cellular stress regulation, including <i>TP53, CDKN1A/p21, APC, VEGF, XPD,</i> and <i>RAD51</i>, in occupational groups exposed to chronic low-dose ionizing radiation at the Stepnogorsk Mining Chemical Combine and the Balkashinskoye uranium deposit. Genotyping was performed using PCR-based assays followed by restriction fragment length polymorphism (RFLP) analysis. Allele and genotype frequencies were compared between radiation-exposed workers and matched controls within Kazakh and Russian ethnic subgroups. Statistical differences were assessed using χ² tests, and associations with radioresistance were interpreted based on established functional characteristics of each polymorphism. <b>Results</b>: Four SNPs showed significant allele and genotype frequency shifts in radiation-exposed populations. The <i>TP53</i> intron 3 insertion allele, <i>TP53</i> intron 6 A allele, <i>TP53</i> Pro72 (C) allele, and p21 codon 31 A allele were consistently enriched among exposed individuals. The strongest deviations were observed in Russian workers from Stepnogorsk (<i>p</i> < 0.01). These alleles are functionally associated with enhanced DNA repair efficiency, modified apoptotic responses, and strengthened cell-cycle checkpoint regulation. <b>Conclusions</b>: Significant enrichment of radioresistance-associated <i>TP53</i> and <i>CDKN1A</i> (p21) variants was observed in uranium industry workers chronically exposed to low-to-moderate ionizing radiation. The observed patterns support a polygenic model of adaptive responses and emphasize the importance of genetic background in determining individual radiosensitivity under occupational exposure conditions.