Association of Interleukin‐17F Polymorphisms (rs763780, rs9382084, rs2397084, and rs12203582) With Gastric Cancer Susceptibility According to Helicobacter pylori Infection Status

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.