Methylation of cell cycle and apoptosis genes’ promoters in exposed individuals with subsequent malignant neoplasms

Abstract

DNA methylation plays an important role in carcinogenesis; there are many studies that investigate the degree of methylation of the entire genome, gene promoters, and non-coding elements in cancer cells, but much less information about changes of the methylation patterns in blood cells and links with the development of malignant neoplasms (MN). This study aimed to investigate the degree of methylation of promoter regions of cell cycle control and apoptosis genes (BAX, MDM2, TP53, NFkB1) in peripheral blood cells of persons chronically exposed to radiation with MN developing latently. The study included 200 persons chronically exposed to radiation from the Techa River, contaminated with nuclear wastes dumped into it. The level of methylation was assessed by real-time PCR. The participants were divided into exposed and control groups; comparing them, we found that in the former, the distribution of exposed individuals with latent MN by the degree of methylation of promoter regions of BAX, MDM2 and NFkB1 genes was significantly different from that in the latter (p < 0.001; p < 0.001; p = 0.004, respectively). It was established that, compared to the control group, the share of the test group participants with subsequent MN who had up to 10% of the BAX gene promoter regions methylated was significantly higher, and amounted to 98%, while in the control group this figure did not exceed 73% (p < 0.00001).