Genome integrity maintaining variants in EGFR gene related to ionizing radiation resistance in the Lithuanian Chornobyl clean-up workers cohort

Background : Ionizing radiation (IR) is a well-known factor that predisposes cells to mutagenesis, cancerous processes, inflammation, oxidative stress, apoptosis, and DNA repair. However, the genetic factors maintaining genome integrity after ionizing radiation exposure are not fully defined. Relatively healthy Lithuanian Chornobyl catastrophe clean-up workers (LCCWs) are a unique study group. We hypothesize that the group’s genomic variation determines their reaction to IR. We aimed to perform the genomic variation analysis of the preselected set of genes that might be involved in genome integrity maintenance. The set consists of six sub-groups of genes representing different molecular mechanisms or pathways (apoptosis, tumor suppression, inflammation, oxidative stress, DNA repair, and regulatory molecules) potentially related to the genome and cell integrity after exposure to high-dose IR. The study group included 38 male LCCWs. The control group consisted of 27 unrelated, not exposed to IR males of Lithuanian descent. Variants of the genes were filtered out from whole-genome short-read sequencing data. Targeted gene-set association analysis was performed using PLINK v1.9 software. Results : The study identified statistically significant ( p =0.0122) associations in the 7p11.2 genomic region spanning the epidermal growth factor receptor ( EGFR ) gene. Conclusion : Analysis showed that variation in the EGFR gene important for DNA repair, apoptosis, and resistance to IR might have specific effects on maintaining genome and cell integrity after exposure to high-dose IR.