Different patterns of allelic imbalance in sporadic tumors and tumors associated with long-term exposure to gamma-radiation

•We compare the prevalence of genotypes of SNP in tumors and matched normal tissues.•We consider the effects of gamma-radiation on the risk of the development of cancer.•We showed the phenomenon of allelic imbalance in tumors associated with radiation.•We demonstrated the phenomenon of allelic imbal...

Full description

Saved in:
Bibliographic Details
Published in:Mutation research. Genetic toxicology and environmental mutagenesis 2015-12, Vol.794, p.8-16
Main Authors: Litviakov, Nikolai V., Freidin, Maxim B., Sazonov, Aleksey E., Khalyuzova, Maria V., Buldakov, Mikhail A., Karbyshev, Mikhail S., Albakh, Еlena N., Isubakova, Daria S., Gagarin, Аleksey A., Nekrasov, Gennadiy B., Mironova, Elena B., Izosimov, Аndrey S., Takhauov, Ravil M., Karpov, Аndrei B.
Format: Article
Language:English
Subjects:
Adult
Aged
Allelic Imbalance
Case-Control Studies
Cell cycle
DNA Repair
Female
Gamma rays
Gamma Rays - adverse effects
Gene Frequency
Genes
Genetic Association Studies
Genetic Loci
Genetic polymorphism
Genotype
Genotype & phenotype
Humans
Male
Malignant tumor
Middle Aged
Mutation
Neoplasms - etiology
Neoplasms - genetics
Occupational Exposure - adverse effects
Polymorphism, Single Nucleotide
Tumors
γ-Radiation
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•We compare the prevalence of genotypes of SNP in tumors and matched normal tissues.•We consider the effects of gamma-radiation on the risk of the development of cancer.•We showed the phenomenon of allelic imbalance in tumors associated with radiation.•We demonstrated the phenomenon of allelic imbalance in spontaneous tumors. 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.
ISSN:1383-5718
1879-3592
DOI:10.1016/j.mrgentox.2015.09.003