Six IL-8 gene polymorphisms and the entire cancer susceptibility according to a comprehensive analysis especially in prostate cancer.

OBJECTIVES: Interleukin-8 (IL-8) is a key cytokine regulating immunity and inflammation, and its genetic polymorphisms have been increasingly linked to cancer susceptibility. However, findings on the role of specific IL-8 polymorphisms across different cancers remain inconsistent, necessitating a comprehensive meta-analysis. METHODS: The authors systematically searched Embase, PubMed, Chinese databases, Google Scholar, and Web of Science up to June 25, 2023. A total of 104 case-control studies (26,029 cases and 31,577 controls) were included in a high-powered meta-analysis. Summary Odds Ratios (ORs) with 95% Confidence Intervals (95% CIs) were calculated using Stata. Additionally, the authors performed an ELISA-based validation study to measure serum IL-8 levels in Prostate Cancer (PCa) patients grouped by genotype. RESULTS: The +2767 polymorphism was associated with a significant reduction in overall cancer risk. The +781 polymorphism increased cancer risk specifically in Caucasian populations. In contrast, the -251 polymorphism demonstrated a strong pan-cancer risk association, particularly in Mixed/Asian ethnicities, gastric cancer, lung cancer, and hospital-based studies. Mechanistically, patients with the -251 AA/AC genotypes had elevated serum IL-8 levels, which were linked to more aggressive PCa pathogenesis. CONCLUSION: This pioneering meta-analysis identifies the IL-8 -251 polymorphism as a high-risk biomarker and +2767 as a protective variant. By functionally validating that the -251 risk allele promotes PCa progression via IL-8 overexpression, the present study establishes IL-8 genotyping as a potential tool for ethnic-specific risk stratification and prognostic prediction, with broad implications for precision oncology.