Systematic analyses of the relationship between five CXCL8 gene polymorphisms and overall cancer risk

Abstract

Background Interleukin-8 (IL-8/CXCL8) is a prototypical CXC family chemokine bearing an ELR motif that plays key roles in the onset and progression of a range of cancers in humans. Many prior studies have focused on exploring the relationship between CXCL8 gene polymorphisms and the risk of cancer. However, the statistical power of many of these reports was limited, yielding ambiguous or conflicting results in many cases. Methods Accordingly, the present meta-analysis of 28 related publications was conducted in an effort to better understand the association between these mutations and disease risk. Results The CXCL8 -353A/T polymorphism was associated with an increased overall cancer risk [A vs. T, odds ratio (OR) = 1.255, 95% confidence interval (CI) (1.079–1.459), Pheterogeneity = 0.449, P = 0.003]. The CXCL8 + 781T/C allele was similarly associated with a higher risk of cancer among Caucasians [TT vs. TC + CC, OR = 1.472, 95%CI (1.078–2.009), Pheterogeneity = 0.366, P = 0.015]. To better clarify the relationship between these mutations and clinical outcomes, tissue samples from oral cancer patients and healthy controls were analyzed. In these analyses, oral cancer patients carrying the CXCL + 781 TT + TC genotypes exhibited pronounced increases in serum levels of CXCL8 as compared to patients carrying the CC genotype (P < 0.01), and CXCL8 levels were also significantly higher in oral cancer patients with these two genotypes as compared to genotype-matched normal controls (P < 0.01). Conclusion These results thus suggest that the CXCL8-353 and + 781 polymorphisms may be associated with a greater risk of cancer development. The + 781 polymorphism may further offer value as a biomarker that can aid in the early identification and prognostic evaluation of oral cancer.