title: Different patterns of allelic imbalance in sporadic tumors and tumors associated with long-term exposure to gamma-radiation.
abstract: The study aimed to reveal cancer related mutations in DNA repair and cell cycle genes associated with chronic occupational exposure to gamma-radiation in personnel of the Siberian Group of Chemical Enterprises (SGCE). Mutations were analyzed by comparing genotypes of malignant tumors and matched normal tissues of 255 cancer patients including 98 exposed to external gamma-radiation (mean dose 128.1±150.5mSv). Also a genetic association analysis was carried out in a sample of 149 cancer patients and 908 healthy controls occupationally exposed to gamma-radiation (153.2±204.6mSv and 150.5±211.2mSv, respectively). Eight SNPs of genes of DNA excision repair were genotyped (rs13181, rs1052133, rs1042522, rs2305427, rs4244285, rs1045642, rs1805419 and rs1801133). The mutation profiles in heterozygous loci for selected SNP were different between sporadic tumors and tumors in patients exposed to radiation. In sporadic tumors, heterozygous genotype Arg/Pro of the rs1042522 SNP mutated into Arg/0 in 15 cases (9.6%) and 0/Pro in 14 cases (8.9%). The genotype Lys/Gln of the rs13181 SNP mutated into Lys/0 and 0/Gln in 9 and 4 cases, respectively. In tumors of patients exposed to low-level radiation, the rs1042522 Arg/0 mutated genotype was found in 12 cases (12.1%), while in 2 cases (2%) 0/Pro mutation was observed. Finally, the rs13181 0/Gln mutated genotype was observed in 15 cases (16,5%) . Thus, our study showed the difference in patterns of allelic imbalance in tumors appeared under low-level radiation exposure and spontaneous tumors for selected SNPs. This suggests different mechanisms of inactivation of heterozygous genotypes in sporadic and radiation-induced tumors.
authors.affiliation: Seversk Biophysical Research Centre of the Federal Medical and Biological Agency, Seversk, Russia; Tomsk Cancer Research Institute, Tomsk, Russia; National Research Tomsk State University, Tomsk, Russia. Electronic address: nvlitv72@yandex.ru.
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Litviakov
authors.affiliation: Population Genetics Laboratory, Research Institute for Medical Genetics, Tomsk, Russia.
authors.forename: Maxim B
authors.initials: MB
authors.lastname: Freidin
authors.affiliation: Seversk Biophysical Research Centre of the Federal Medical and Biological Agency, Seversk, Russia.
authors.forename: Aleksey E
authors.initials: AE
authors.lastname: Sazonov
authors.affiliation: Seversk Biophysical Research Centre of the Federal Medical and Biological Agency, Seversk, Russia; National Research Tomsk State University, Tomsk, Russia.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Khalyuzova
authors.affiliation: Tomsk Cancer Research Institute, Tomsk, Russia; National Research Tomsk State University, Tomsk, Russia.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Buldakov
authors.affiliation: Tomsk Cancer Research Institute, Tomsk, Russia; National Research Tomsk State University, Tomsk, Russia.
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Karbyshev
authors.affiliation: Seversk Biophysical Research Centre of the Federal Medical and Biological Agency, Seversk, Russia.
authors.forename: Еlena N
authors.initials: ЕN
authors.lastname: Albakh
authors.affiliation: Seversk Biophysical Research Centre of the Federal Medical and Biological Agency, Seversk, Russia.
authors.forename: Daria S
authors.initials: DS
authors.lastname: Isubakova
authors.affiliation: Clinical Hospital #81 of the Federal Medical and Biological Agency, Seversk, Russia.
authors.forename: Аleksey A
authors.initials: АA
authors.lastname: Gagarin
authors.affiliation: Clinical Hospital #81 of the Federal Medical and Biological Agency, Seversk, Russia.
authors.forename: Gennadiy B
authors.initials: GB
authors.lastname: Nekrasov
authors.affiliation: Clinical Hospital #81 of the Federal Medical and Biological Agency, Seversk, Russia.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Mironova
authors.affiliation: Clinical Hospital #81 of the Federal Medical and Biological Agency, Seversk, Russia.
authors.forename: Аndrey S
authors.initials: АS
authors.lastname: Izosimov
authors.affiliation: Seversk Biophysical Research Centre of the Federal Medical and Biological Agency, Seversk, Russia.
authors.forename: Ravil M
authors.initials: RM
authors.lastname: Takhauov
authors.affiliation: Seversk Biophysical Research Centre of the Federal Medical and Biological Agency, Seversk, Russia.
authors.forename: Аndrei B
authors.initials: АB
authors.lastname: Karpov
mesh_terms: D000328:Adult; D000368:Aged; D022981:Allelic Imbalance; D016022:Case-Control Studies; D004260:DNA Repair; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide
keywords: Allelic imbalance; Genetic polymorphism; Malignant tumor; γ-Radiation