Associations of the -238(G/A) and -308(G/A) TNF-α Promoter Polymorphisms and TNF-α Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to Helicobacter pylori Infection in a Moroccan Population

Association des polymorphismes -238(G/A) et -308(G/A) du promoteur du TNF alpha et des taux sériques de TNF alpha avec la susceptibilité aux lésions précancéreuses et cancéreuses gastriques associées à l'infection par Helicobacter pylori dans la population Marocaine.

Ghizlane Bounder (1, 2) , Mohamed Reda Jouimyi (1, 2) , Hasna Boura (1) , Eliette Touati (3) , Valérie Michel (3) , Wafaa Badre (4) , Hassan Jouhadi (4) , Maria Kadi (4) , Meriem Eljihad (4) , Hakima Benomar (1) , Anass Kettani (2) , Halima Lebrazi (2) , Fatima Maachi (1)

1 Institut Pasteur du Maroc
2 Faculté des Sciences Ben M'sik [Casablanca]
3 Pathogenèse de Helicobacter
4 CHU Ibn Rochd [Casablanca]

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Keywords: Helicobacter ‎pylori.‎; TNFα polymorphisms; TNFα serum levels; gastric carcinogenesis

Domains: Cancer; Human genetics; Infectious diseases

Ghizlane Bounder, Mohamed Reda Jouimyi, Hasna Boura, Eliette Touati, Valérie Michel, et al.. Associations of the -238(G/A) and -308(G/A) TNF-α Promoter Polymorphisms and TNF-α Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to Helicobacter pylori Infection in a Moroccan Population. Asian Pacific Journal of Cancer Prevention, 2020, 21 (6), pp.1623-1629. ⟨10.31557/APJCP.2020.21.6.1623⟩. ⟨pasteur-02914611⟩