Helicobacter Pylori and Gastric Pathologies Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.
Biology and Health Laboratory, Faculty of Sciences Ben M'sik, University Hassan II, Casablanca, Morocco.
Asian Pac J Cancer Prev. 2020 Jun 1;21(6):1623-1629. doi: 10.31557/APJCP.2020.21.6.1623.
Helicobacter pylori (H. pylori) induces the production of tumor necrosis factor-alpha (TNF-α), which is closely related to a gastric epithelial injury. TNF-α gene polymorphism and TNF-α serum levels are associated with various malignant conditions. Identification of the ideal marker for gastric cancer (GC) is still the leading aim of several trials. Physio-pathological considerations of GC led us to investigate the association of two TNF-α promoter polymorphisms (-308G>A and -238G>A), and TNF-α serum levels with the susceptibility to gastric precancerous (PL) and GC.
Patients suffering from gastric lesions (65 chronic gastritis, 50 PL, 40 GC) related to H. pylori infection , and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNF-α gene promoter sequencing and TNF-α serum levels are measured by ELISA quantitative method.
Regarding TNF-α-308 G/A locus, we noticed higher risk for GC (OR=4.3, CI 1.5-11.9, p-value=0.005) and PL (OR=3.4, CI 1.2-9.2, p-value=0.01) for individuals with AA/GA genotypes compared to GG genotype. Concerning TNF-α-238 G/A locus, we noticed higher risk for GC (OR=5.9, CI 1.2-27.5, p-value=0.01) and PL (OR=4.8, CI 1.3-18, p-value=0.01) for individuals with GG genotype compared to AA/GA genotypes. We noticed that TNF-α serum levels have been increased together with gastric lesions severity. Moreover, TNF-α-308 and TNF-α-238 A alleles seemed to, respectively, upregulate and downregulate TNF-α serum levels.
The TNF-α -308 A allele has a promotive effect for GC progression, whereas the TNF-α -238 A allele has a protective function against GC progression. High levels of TNF-α seemed to be associated with the aggressiveness of gastric lesions. TNF-α gene polymorphisms and TNF-α serum levels might be helpful to select those patients who are at high risk for GC.
幽门螺杆菌（H. pylori）诱导肿瘤坏死因子-α（TNF-α）的产生，而 TNF-α 与胃上皮损伤密切相关。TNF-α 基因多态性和 TNF-α 血清水平与各种恶性疾病有关。寻找理想的胃癌（GC）标志物仍然是多项试验的主要目标。GC 的病理生理学考虑促使我们研究 TNF-α 启动子两个多态性（-308G>A 和 -238G>A）和 TNF-α 血清水平与胃癌前病变（PL）和 GC 易感性的关联。
本研究纳入了 65 例慢性胃炎、50 例 PL、40 例 GC 相关的胃病变患者和 63 例健康对照者（HC）。通过 TNF-α 基因启动子测序对个体进行基因分型，并通过 ELISA 定量法测量 TNF-α 血清水平。
在 TNF-α-308 G/A 位点，与 GG 基因型相比，AA/GA 基因型个体的 GC（OR=4.3，CI 1.5-11.9，p 值=0.005）和 PL（OR=3.4，CI 1.2-9.2，p 值=0.01）风险更高。在 TNF-α-238 G/A 位点，与 AA/GA 基因型相比，GG 基因型个体的 GC（OR=5.9，CI 1.2-27.5，p 值=0.01）和 PL（OR=4.8，CI 1.3-18，p 值=0.01）风险更高。我们注意到，随着胃病变严重程度的增加，TNF-α 血清水平也升高。此外，TNF-α-308 和 TNF-α-238 A 等位基因似乎分别上调和下调 TNF-α 血清水平。
TNF-α-308 A 等位基因对 GC 进展具有促进作用，而 TNF-α-238 A 等位基因对 GC 进展具有保护作用。TNF-α 血清水平与胃病变的侵袭性相关。TNF-α 基因多态性和 TNF-α 血清水平可能有助于选择 GC 高危患者。
