title: 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.
authors.affiliation: a Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, 80937 Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Abend
authors.forename: Tamara
authors.initials: T
authors.lastname: Azizova
authors.forename: Kerstin
authors.initials: K
authors.lastname: Müller
authors.forename: Harald
authors.initials: H
authors.lastname: Dörr
authors.forename: Sven
authors.initials: S
authors.lastname: Doucha-Senf
authors.forename: Helmut
authors.initials: H
authors.lastname: Kreppel
authors.forename: Galina
authors.initials: G
authors.lastname: Rusinova
authors.forename: Irina
authors.initials: I
authors.lastname: Glazkova
authors.forename: Natalia
authors.initials: N
authors.lastname: Vyazovskaya
authors.forename: Kristian
authors.initials: K
authors.lastname: Unger
authors.forename: Herbert
authors.initials: H
authors.lastname: Braselmann
authors.forename: Viktor
authors.initials: V
authors.lastname: Meineke
mesh_terms: D002908:Chronic Disease / Q000453:epidemiology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D055848:Nuclear Power Plants; D016273:Occupational Exposure; D012333:RNA, Messenger / Q000096:biosynthesis; D011832:Radiation Injuries; D012426:Russia
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger