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

## TL;DR

This study identifies specific IL-8 gene polymorphisms that are linked to cancer risk, particularly in prostate cancer, and suggests they could be used as biomarkers for cancer detection.

## Contribution

The study functionally validates the IL-8 -251 polymorphism as a high-risk biomarker for prostate cancer progression.

## Key findings

- The -251 polymorphism is strongly associated with increased cancer risk across multiple cancer types.
- The -251 AA/AC genotypes are linked to higher IL-8 expression and more aggressive prostate cancer.
- The +2767 polymorphism is associated with reduced overall cancer risk.

## Abstract

•+2767, +781, and −251 polymorphisms were associated with cancer risk.•−251 variant may directly influence IL-8 expression in prostate cancer patients.•These polymorphisms represent promising candidate biomarkers of cancer detection.

+2767, +781, and −251 polymorphisms were associated with cancer risk.

−251 variant may directly influence IL-8 expression in prostate cancer patients.

These polymorphisms represent promising candidate biomarkers of cancer detection.

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.

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.

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.

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.