Effect of Repair Gene Polymorphism on the Risk of Malignant Neoplasm Development after Chronic Radiation Exposure.

IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
E A Blinova, A V Korechenkova, M A Yanishevskaya, A V Akleyev
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引用次数: 0

Abstract

The efficiency of DNA integrity repair processes after radiation exposure may depend on hereditary variations of repair genes caused by single nucleotide polymorphisms. Disturbances or even failure of repair processes trigger a chain of reactions leading to genome instability and oncogenic transformation of the cell.

Objective: : To investigate the association of single nucleotide polymorphism in genes of nucleotide excision repair (ERCC2 rs13 181, XPC rs2 228 001), AP site repair (APEX rs1 130 409), homologous recombination (XRCC3 rs861 539), single-strand DNA break repair (XRCC1 rs25 487), and double-strand DNA break repair (PARP rs1 136 410, XRCC4 rs2 075 685) with the risk of malignant neoplasm development of various localisations in chronically exposed persons.

Materials and methods: . The study was conducted in 861 persons who were exposed to chronic low dose rate radiation, 274 of which had malignant neoplasms (MN) of various localisations and 587 made up the comparison group (exposed persons without MN). The mean accumulated dose to red bone marrow (RBM) in the group of persons with MN was 561.65 ± 25.31 mGy, while in the comparison group it was 543.14 ± 36.06 mGy. Genotyping of polymorphic loci rs13181, rs2 228 001, rs1130409, rs861 539, rs25 487, rs1136410, and rs2075685 was performed by real-time PCR. The association of polymorphic loci with the risk of MN development was determined by the odds ratio (OR) and 95% confidence interval (95% CI). A multifactor dimensionality reduction method was used to assess intergenic interactions.

Results: : Single-stranded DNA break repair gene (XRCC1) rs25 487 polymorphism in accordance with the dominant model is associated with an increased risk of MN development in the combined group of the examined persons (OR = 1.79 (1.12-2.87), p = 0.01). The polymorphism of the gene involved in homologous recombination rs861539 (XRCC3) in accordance with the recessive model is associated with a reduced risk of MN development both in the combined group of exposed persons (OR = 0.25 (0.15-0.41; p < 0.00001), and separately in the group of the Slavs (OR = 0.28 (0.13-0.60); p < 0.0001) and in the group of the Turkic people (OR = 0.22 (0.11-0.44); p < 0.0001). The model of interfactorial interactions allowed us to establish a protective effect with respect to the risk of MN development in carriers of polymorphic loci rs861539 of the XRCC3 gene and rs1130409 of the APEX1 gene (p < 0.001).

修复基因多态性对慢性辐射照射后恶性肿瘤发生风险的影响。
辐射暴露后DNA完整性修复过程的效率可能取决于由单核苷酸多态性引起的修复基因的遗传变异。修复过程的干扰甚至失败会引发一系列反应,导致基因组不稳定和细胞的致癌转化。目的:探讨慢性暴露人群中核苷酸切除修复基因(ERCC2 rs13 181、XPC rs2 228 001)、AP位点修复基因(APEX rs1 130 409)、同源重组基因(XRCC3 rs861 539)、单链DNA断裂修复基因(XRCC1 rs25 487)、双链DNA断裂修复基因(PARP rs1 136 410、XRCC4 rs2 075 685)的单核苷酸多态性与不同部位恶性肿瘤发生风险的关系。材料与方法:。该研究在861名慢性低剂量率辐射暴露者中进行,其中274人患有不同部位的恶性肿瘤(MN), 587人组成对照组(没有MN的暴露者)。MN组红骨髓累积剂量(RBM)为561.65±25.31 mGy,对照组为543.14±36.06 mGy。对rs13181、rs2 228 001、rs1130409、rs861 539、rs25 487、rs1136410和rs2075685位点进行实时荧光定量PCR分型。通过比值比(OR)和95%置信区间(95% CI)确定多态性位点与MN发生风险的关联。采用多因素降维方法评估基因间相互作用。结果:单链DNA断裂修复基因(XRCC1) rs25 487多态性符合显性模型,与联合组患者MN发生风险增加相关(OR = 1.79 (1.12-2.87), p = 0.01)。根据隐性模型,参与同源重组rs861539 (XRCC3)的基因多态性与暴露者联合组中MN发生风险降低相关(OR = 0.25 (0.15-0.41;p < 0.00001),斯拉夫人组(OR = 0.28 (0.13-0.60);p < 0.0001)和突厥人组(OR = 0.22 (0.11-0.44);P < 0.0001)。因子间相互作用模型使我们能够在XRCC3基因多态性位点rs861539和APEX1基因多态性位点rs1130409的携带者中建立MN发展风险的保护作用(p < 0.001)。
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来源期刊
Doklady Biochemistry and Biophysics
Doklady Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
1.60
自引率
12.50%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.
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