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硒、镉和砷水平与胃癌和非癌组织中 DNA 修复基因(XRCC5、XRCC6)遗传多态性的关系。

Association between selenium, cadmium, and arsenic levels and genetic polymorphisms in DNA repair genes (XRCC5, XRCC6) in gastric cancerous and non-cancerous tissue.

机构信息

Metabolic disorders research center, Golestan University of Medical Sciences, Gorgan, Iran.

Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran.

出版信息

J Trace Elem Med Biol. 2019 Sep;55:89-95. doi: 10.1016/j.jtemb.2019.06.003. Epub 2019 Jun 12.

DOI:10.1016/j.jtemb.2019.06.003
PMID:31345372
Abstract

Gastric cancer is one of the most prevalent cancers in northern Iran. The DNA repair genes X-ray repair cross-complementing (XRCC) group 5, XRCC6, which are important members of non-homologous end-joining repair system, play an important role in repairing the DNA double-strand breaks. Chronic exposure to heavy metals has long been recognized as being capable of augmenting gastric cancer incidence among exposed human populations. Since trace elements could directly or indirectly damage DNA, and polymorphism in DNA DSBs-repair genes can alter the capacity of system repair, we assumed that XRCC5 VNTR and XRCC6-61C >G polymorphism also impress the DSBs-repair system ability and contribute to gastric cancer. Therefore, the objective of this research was to evaluate the tissue accumulation of Selenium (Se), Cadmium (Cd) and Arsenic (As), and XRCC5 VNTR, XRCC6-61C >G polymorphisms in cancerous and non-cancerous tissues in Golestan province. The study population included 46 gastric cancer patients and 43 cancer-free controls. Two polymorphisms of XRCC5, XRCC6 were genotyped using polymerase chain reaction (PCR) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Further employed was atomic absorption spectroscopy so as to determine the levels of Se, Cd and As. Finally, the data were analyzed by SPSS (version 16) statistical software. The Se level was significantly higher in tumors as compared to non-tumor tissues, but there was no significant correlation between As and Cd in cancerous and noncancerous tissues. Allele frequencies of the selected genes were not statistically different between groups regarding XRCC6 (-61C>G). XRCC5 0R/0R, 0R/1R, 1R/1R, and 0R/2R genotypes were more common in cancerous group. High levels of Se in cancerous tissues vs. non-cancerous tissues may be one of the carcinogenic factors; in Golestan province, unlike other regions of Iran and the world, the level of Se is high, hence the higher risks of gastric cancer.

摘要

胃癌是伊朗北部最常见的癌症之一。X 射线修复交叉互补基因 5(XRCC)组 5、XRCC6 是非同源末端连接修复系统的重要成员,在修复 DNA 双链断裂方面发挥着重要作用。长期以来,人们一直认为慢性暴露于重金属会增加暴露人群的胃癌发病率。由于微量元素可以直接或间接损伤 DNA,并且 DNA 双链断裂修复基因的多态性可以改变系统修复的能力,因此我们假设 XRCC5 VNTR 和 XRCC6-61C>G 多态性也会影响 DSBs 修复系统的能力,并导致胃癌。因此,本研究旨在评估戈尔斯坦省癌组织和非癌组织中硒(Se)、镉(Cd)和砷(As)的组织蓄积以及 XRCC5 VNTR、XRCC6-61C>G 多态性。研究人群包括 46 例胃癌患者和 43 例无癌对照。采用聚合酶链反应(PCR)或聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对 XRCC5、XRCC6 两种多态性进行基因分型。进一步采用原子吸收光谱法测定 Se、Cd 和 As 水平。最后,采用 SPSS(版本 16)统计软件进行数据分析。与非肿瘤组织相比,肿瘤组织中的 Se 水平显著升高,但癌组织和非癌组织中的 As 和 Cd 之间无显著相关性。在 XRCC6(-61C>G)方面,所选基因的等位基因频率在组间无统计学差异。癌症组中 XRCC5 0R/0R、0R/1R、1R/1R 和 0R/2R 基因型更为常见。与非癌组织相比,癌组织中 Se 水平较高可能是致癌因素之一;在戈尔斯坦省,与伊朗和世界其他地区不同,Se 水平较高,因此胃癌风险较高。

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