Archives2023Vol. 63, № 1pp. 60-70

Article

Association Between Single Nucleotide Polymorphisms of Apoptosis and Cell Cycle Control Genes and the Risk of Cancer Development in Chronically Exposed Persons

E. A. Blinova1,2, M. A. Yanishevskaya1, A. V. Korechenkova1, A. V. Akleyev1,2

1Urals Research Center for Radiation Medicine, Chelyabinsk, Russia 2Chelyabinsk State University, Chelyabinsk, Russia

Abstract

The objective of the paper was to study the association between single nucleotide polymorphisms of genes involved in the cell cycle control (ATM rs664677, MDM2 rs2279744, CDKN1A rs1801270) and apoptosis (BCL-2 rs2279115, BAX rs4645878, TNFα rs361525) and the risk of solid cancer development in persons of different ethnicity exposed to chronic radiation. The study included 915 residents of the Techa riverside settlements belonging to two ethnic groups (Slavs and Turks) who were affected by chronic low dose rate exposure in the low to and medium dose range. 310 persons out of them had solid cancers. Genotyping of polymorphic regions of genes regulating cell cycle and apoptosis was performed by real-time PCR method. The study showed that the rs2279744*C allele of the MDM2 gene was associated with an increased risk of cancer development (OR = 2.29; 95% CI 1.23–4.28; p = 0.007), while the rs1801270*A allele of the CDKN1A gene showed a protective effect against cancer development (OR = 0.55; 95% CI 0.35–0.85; p = 0.01) in exposed individuals of the Turkic ethnic group. The combined effect of the identified polymorphisms and soft tissue exposure dose statistically significantly modifies the risk of cancer development in chronically exposed persons of the Turkic ethnic group, with the greatest contribution being made by the carriage of the rs2279744*C allele of the MDM2 gene.

Keywords

Carcinogenic effects, chronic exposure, single nucleotide polymorphisms, cancer risk

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