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Purpose: To conduct genome wide association study of the association of 750,000 SNPs and an increased frequency of different types of chromosomal aberrations, induced by chronic irradiation in the dose range of 100–300 mSv. Material and methods: The study was conducted among Siberian Group of Chemical Enterprises healthy employees (n = 37) exposed to professional external γ-radiation in a dose range of 100–300 mSv. The de novo induced CNVs were previously detected in these persons. Mean dose – 188.8 ± 8.3 mSv, median – 185 mSv, interquartile range – 147.8–218.7 mSv, min – 103.4 mSv, max – 295.8 mSv. Genotyping of DNA samples from 37 employees was carried out by microarray CytoScan™ HD Array (Affymetrix, USA), containing 750,000 SNP-markers of 36,000 genes. The standard cytogenetic analysis was performed in the entire examined group. Results: We analyzed the association of these SNPs with the frequencies of aberrant cells and following chromosomal aberrations: single chromatid fragments, chromatid exchanges, paired fragments, dicentrics, rings, and translocations. We have found that 8 SNPs (rs10779468, rs158735, rs158710, rs158712, rs11131536, rs528170, rs9533572, rs10512439) are associated with the frequency of aberrant cells. Conclusion: We have discovered polymorphic variants that are associated with an increased frequency of aberrant cells in workers of Siberian Group of Chemical Enterprises exposed to irradiation at a dose of 100–300 mSv. This polymorphic variants can be considered as potential markers of individual radiosensitivity. To confirm identified associations, further validation studies on an extended sample of people exposed to radiation are needed.

The results from the selective validation research into the association between genetic polymorphisms and the frequency of cytogenetic abnormalities on a large independent sample are analyzed. These polymorphisms have been identified previously during own microarray studies. It has been shown an association with the frequency of dicentric and ring chromosomes induced by radiation exposure. The study was conducted among Siberian Group of Chemical Enterprises healthy employees (n = 573) exposed to professional irradiation in a dose range of 40–400 mSv. We have found that 5 SNP are confirmed to be associated with the frequency of dicentric and ring: INSR rs1051690 – insulin receptor gene; WRNrs2725349 – Werner syndrome gene, RecQ helicase-like; VCAM1 rs1041163 – vascular cell adhesion molecule 1 gene; PCTP rs2114443 – phosphatidylcholine transfer protein gene; TNKS rs7462102 – tankyrase gene; TRF1-interacting ankyrin-related ADP-ribose polymerase. IGF1 rs2373721 – insulin-like growth factor 1 gene has not confirmed to be associated with the frequency of dicentric and ring chromosomes.