Mikaela Nagahara, Bruno Mari Fredi, Fabricio Abdalla BRANDT, Alanis dos Santos Fonseca, Milena Milani Coelho, Danielli Girolli, Elizabeth Suchi Chen, Mônica Santiago Barbosa, Spencer Luíz Marques Payão, Lucas Trevizani Rasmussen
Single nucleotide polymorphisms (SNPs) in the interleukin-17F (IL-17F) gene may modulate inflammatory responses, with distinct effects on inflammation and tumour progression. Helicobacter pylori infection, a Group 1 carcinogen, is strongly associated with gastric cancer (GC) development. This study investigated the influence of IL-17F SNPs rs763780 (T>C), rs2397084 (T>C), rs9382084 (G>T), and rs12203582 (G>A) on GC susceptibility, considering H. pylori infection status. A total of 301 gastric biopsy samples were classified into the control (n = 95), gastritis (n = 112), and cancer (n = 94) groups. Helicobacter pylori detection and SNP genotyping were performed by quantitative real-time PCR (qPCR). Statistical analyses included Hardy-Weinberg equilibrium (HWE), Fisher's exact test, haplotype analysis, and genetic models using the SNPStats software, with sensitivity analysis performed in G*Power. All SNPs conformed to HWE except for rs763780. The T/C genotype and C allele of rs763780 were more frequent in the control group, indicating a protective effect (OR = 0.35; 95% CI = 0.14-0.91; p = 0.04). In contrast, the G/G genotype of rs9382084 (OR = 2.29; 95% CI = 1.02-5.13; p = 0.039) and the A/A genotype of rs12203582 (OR = 3.01; 95% CI = 1.01-8.93; p = 0.047) were associated with increased GC risk. No significant association was found for rs2397084. Haplotype analysis identified the rs763780-C/rs2397084-T/rs9382084-T/rs12203582-G haplotype as protective against GC (OR = 0.30; 95% CI = 0.10-0.86; p = 0.026). Stratified analysis according to H. pylori infection status suggested specific associations between SNPs rs763780, rs2397084, and rs12203582 and the risk of GC. These findings suggest that IL-17F gene SNPs influence GC susceptibility, exerting protective or risk effects depending on the specific polymorphism and its interaction with H. pylori infection.