The contribution of interleukin-8 genotypes and expression to nasopharyngeal cancer susceptibility in Taiwan

Abstract

The incidence rate of nasopharyngeal cancer (nasopharyngeal carcinoma [NPC]) is much higher in Southeast Asia than in western countries. Interleukin-8 (IL-8), a chemokine produced by macrophages, epithelial cells, airway smooth muscle cells, and endothelial cells, is an important immuno-mediator in the development and progression of many types of cancer. Genetic variations in IL-8 have been associated with the risks of NPC and other cancers. In the current study, we evaluated the role of IL-8 in NPC at the levels of DNA, RNA, and protein in a Taiwanese population. First, in a case-control study, 176 NPC patients and 352 cancer-free controls were genotyped, and the associations of IL-8 T - 251A, C + 781T, C + 1633T, and A + 2767T polymorphisms with NPC risk were evaluated. Second, the NPC tissue samples were assessed for their IL-8 mRNA and protein expression by real-time quantitative reverse transcription polymerase chain reaction (PCR) and Western blotting, respectively. Regarding the IL-8 promoter T - 251A, the TA and AA genotypes were associated with significantly decreased risks of NPC compared with the wild-type TT genotype (adjusted odds ratio = 0.61 and 0.52, 95% confidence interval = 0.47-0.93 and 0.37-0.91, P = .0415 and .0289, respectively). The mRNA and protein expression levels for NPC tissues revealed no significant associations among the 20 NPC samples with different genotypes. These findings suggest that IL-8 may play an important role in the carcinogenesis of NPC in Taiwan.

Figure 1

Analysis of IL-8 mRNA expression levels among nasopharyngeal carcinoma (NPC) patients. (A) Quantitative RT-PCR of NPC tissue samples for the three genotypes of IL-8 promoter T–251A was performed. GAPDH was used as an internal quantitative control. Fold changes were normalized using the levels of GAPDH expression, and each assay was performed at least in triplicate. (B) The TA and AA groups were combined and compared with the TT group. GAPDH = glyceraldehyde.

Figure 2

The expression levels of IL-8 in nasopharyngeal carcinoma (NPC) tissues from patients with different IL-8 promoter T–251A genotypes. (A) Western blotting analysis of IL-8 expression in tumor tissues from cases with TT, TA, and AA IL-8 promoter T–251A genotypes. (B) Quantification of the Western blotting data from (A). β-actin was used as the loading control. Data were averaged from at least 3 repeat analyses of the tissues of each group, with 15 μg total sample protein for each lane.