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Association of Tumor Necrosis Factor Receptor 1 Promoter Gene Polymorphisms (-580 A/G and -609 G/T) and TNFR1 Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to H. pylori Infection in a Moroccan Population
BioMed Research International ( IF 2.6 ) Pub Date : 2020-09-24 , DOI: 10.1155/2020/2451854
Ghizlane Bounder 1, 2 , Mohamed R. Jouimyi 1, 2 , Hasna Boura 1 , Hassan Jouhadi 3 , Wafaa Badre 4 , Hakima Benomar 5 , Anass Kettani 2 , Halima Lebrazi 2 , Fatima Maachi 1
Affiliation  

Chronic inflammation due to H. pylori infection is the risk factor of gastric cancer (GC). Through its receptor (TNFR1), TNF-α plays a fundamental role in inflammatory, infectious, and tumor processes. Dysregulation of TNFR1 gene expression could impact many biological processes that can lead to cancer. This study is aimed at evaluating the association of TNFR1 promoter gene polymorphisms (-580 A/G and -609 G/T) and TNFR1 serum levels with GC and precancerous lesion susceptibility. Patients suffering from gastric lesions (65 chronic gastritis, 50 precancerous lesions, and 40 GC) related to H. pylori infection and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNFR1 gene promoter sequencing, and TNFR1 serum levels were measured by the ELISA quantitative method. Concerning TNFR1 -609 G/T locus, we noticed that the T allele was associated with an attenuated susceptibility to GC (; value = 0.02). At the genotypic level and under the recessive model, the TNFR1 -609 TT genotype showed a decreased risk of GC (, value = 0.03) compared to the combined (GG/GT) genotypes. TNFR1 serum levels have been increased together with gastric lesion severity ( value < 0.05). The TNFR1 -609 TT genotype seemed linked to a low level of sTNFR1 compared to GT and GG genotypes ( value = 0.07). Concerning TNFR1 -580 A/G locus, no significant relation was noticed between this polymorphism and GC susceptibility, as well as with the TNFR1 serum level. Our results suggest that the TNFR1 -609 T allele appears to have a protective effect against GC. High levels of TNFR1 serum levels seemed to be associated with the aggressiveness of gastric lesions. Therefore, our results suggest that TNFR1 -609 T/G polymorphism and the TNFR1 serum levels may be related to GC susceptibility.

中文翻译:

肿瘤坏死因子受体1启动子基因多态性(-580 A / G和-609 G / T)和TNFR1血清水平与摩洛哥人群幽门螺杆菌感染相关的胃癌前病变和胃癌的相关性

幽门螺杆菌感染引起的慢性炎症是胃癌(GC)的危险因素。TNF- α通过其受体(TNFR1)在炎症,感染和肿瘤过程中起着基本作用。TNFR1基因表达失调可能影响许多可能导致癌症的生物学过程。这项研究旨在评估TNFR1启动子基因多态性(-580 A / G和-609 G / T)和TNFR1血清水平与GC和癌前病变易感性的关系。从患者的胃损伤患(65个慢性胃炎,50个癌前病变,和40 GC)相关的幽门螺旋杆菌感染和63位健康对照(HC)参与了这项研究。通过TNFR1基因启动子测序对个体进行基因分型,并通过ELISA定量方法测量TNFR1血清水平。关于TNFR1 -609 G / T基因座,我们注意到T等位基因与对GC的敏感性降低有关(; 值= 0.02)。在基因型水平和隐性模型下,TNFR1 -609 TT基因型显示GC风险降低( 值= 0.03)与组合(GG / GT)基因型相比。TNFR1血清水平和胃部病变严重程度均升高(值<0.05)。与GT和GG基因型相比,TNFR1-609 TT基因型似乎与sTNFR1水平低有关(值= 0.07)。关于TNFR1 -580 A / G基因座,这种多态性与GC敏感性以及与TNFR1血清水平之间没有显着关系。我们的结果表明,TNFR1 -609 T等位基因似乎对GC具有保护作用。TNFR1血清水平高似乎与胃部病变的侵袭性有关。因此,我们的结果表明TNFR1 -609 T / G多态性和TNFR1血清水平可能与GC敏感性有关。
更新日期:2020-09-24
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