The Significant Impacts of Interleukin-8 Genotypes on the Risk of Colorectal Cancer in Taiwan

SIMPLE SUMMARY: The objective of this study was to investigate the association between IL-8 rs4073, rs2227306, rs2227543, and rs1126647 genotypes and the risk of colorectal cancer (CRC) in the Taiwanese population. Our findings reveal that the A allele and AA genotype of IL-8 rs4073 are significantly associated with an increased susceptibility to CRC in Taiwan. This observation provides further evidence of the complex interplay between inflammation and carcinogenesis in CRC development. Furthermore, individuals with the AA genotype exhibit significantly higher levels of serum IL-8 expression. Combining IL-8 rs4073 genotyping with the assessment of IL-8 levels may have potential benefits in terms of the precise risk evaluation and early detection of CRC among patients. ABSTRACT: Interleukin-8 (IL-8), a pro-inflammatory cytokine, is upregulated in CRC and plays an important role in its development and progression. Genetic variants in the IL-8 gene may impact the risk of CRC by modulating IL-8 levels. Our primary objective was to investigate the role of IL-8 genotypes in the development of CRC. To accomplish this, we employed the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze the genotypes of IL-8 rs4017, rs2227306, rs2227543, and rs1126647 in 362 CRC patients and 362 controls. Additionally, we evaluated the interactions between these genotypes and factors such as age, gender, smoking, alcohol consumption, and body mass index (BMI) status in relation to the risk of CRC. Furthermore, we utilized quantitative reverse transcription-PCR to measure the serum IL-8. The results demonstrated a significant difference in the distribution of rs4017 genotypes between the control and case groups (p for trend = 0.0059). Logistic regression analysis revealed that individuals with variant AA genotype had a 1.92-fold higher CRC risk (95% confidence interval [CI] = 1.28–2.89, p = 0.0023). Moreover, carriers of the IL-8 rs4017 AT + AA genotypes exhibited a significant association with CRC risk (odds ratio [OR] = 1.39, 95% CI = 1.02–1.91, p = 0.0460). Additionally, individuals with IL-8 rs4017 AA genotype displayed significantly elevated serum IL-8 compared to those with TT genotype at a 1.73–fold level (p < 0.0001), indicating a correlation between genotype and phenotype. In conclusion, the genotypes of IL-8 rs4017, along with their associated expression levels, can potentially serve as predictive markers for the risk of CRC.