Association of Radiation-Induced Genes with Noncancer Chronic Diseases in Mayak Workers Occupationally Exposed to Prolonged Radiation

Abstract

We examined the association of gene expression with noncancer chronic disease outcomes in Mayak nuclear weapons plant workers who were exposed to radiation due to their occupation. We conducted a cross-sectional study with selection based on radiation exposure status of Mayak plant workers living in Ozyorsk who were alive in 2011 and either exposed to: combined incorporated Plutonium-239 ((239)Pu) and external gamma-ray exposure (n = 82); external gamma-ray exposure alone (n = 18); or were unexposed (n = 50) of Ozyorsk residents who provided community-based professional support for plant personnel and who were alive in 2011. Peripheral blood was taken and RNA was isolated and then converted into cDNA and stored at -20°C. In a previous analysis we screened the whole genome for radiation-associated candidate genes, and validated 15 mRNAs and 15 microRNAs using qRT-PCR. In the current analysis we examined the association of these genes with 15 different chronic diseases on 92 samples (47 males, 45 females). We examined the radiation-to-gene and gene-to-disease associations in statistical models stratified by gender and separately for each disease and exposure. We modeled radiation exposure as gamma or (239)Pu on both the continuous and categorical scales. Unconditional logistic regression was used to calculate odds ratios (OR), 95% confidence intervals (CI), and the concordance for genes that were significantly associated with radiation exposure and a specific disease outcome were identified. Altogether 12 mRNAs and 9 microRNAs appeared to be significantly associated with 6 diseases, including thyroid diseases (3 genes, OR: 1.2-5.1, concordance: 71-78%), atherosclerotic diseases (4 genes, OR: 2.5-10, concordance: 70-75%), kidney diseases (6 genes, OR: 1.3-8.6, concordance: 69-85%), cholelithiasis (3 genes, OR: 0.2-0.3, concordance: 74-75%), benign tumors [1 gene (AGAP4), OR: 3.7, concordance: 81%] and chronic radiation syndrome (4 genes, OR: 2.5-4.3, concordance: 70-99%). Further associations were found for systolic blood pressure (6 genes, OR: 3.7-10.6, concordance: 81-88%) and body mass index [1 gene (miR-484), OR: 3.7, concordance: 81%]. All associations were gender and exposure dependent. These findings suggest that gene expression changes observed after occupational prolonged radiation exposures may increase the risk for certain noncancer chronic diseases.

Pre-Exposure Gene Expression in Baboons with and without Pancytopenia after Radiation Exposure

“…Interestingly, in previous work we had identified HNRPA1 and WNT3 as radiation-induced genes. HNRPA1 , belonging to the hnRNP-family, appeared to be involved in atherosclerotic processes in Mayak workers with internal plutonium exposure [24]. WNT3 was identified as a robust bioindicator that predicted more severe HARS in the first two days after exposure in baboons [12].…”

Transcriptome Alterations In X-Irradiated Human Gingiva Fibroblasts

“…In addition, the results presented here repeatedly showed the overrepresentation of microRNA-genes. Interestingly, deregulation of microRNA gene expression was noted in leukocytes of chronically radiation-exposed humans ( Abend et al 2015 ).…”

Ionizing radiation biomarkers in epidemiological studies – An update

“…Twelve mRNAs and nine miRNAs were significantly associated with six different diseases, particularly those related to atherosclerotic processes. These associations were gender-and dose-dependent and 26 potential confounders were considered including age at exposure, age at biosampling, demographic, social habits, data related to health status [161]. Other studies found long-term changes in gene expression in medical workers [162,163], and in thyroid cancer tissue from patients exposed to Chernobyl fallout [164,165].…”