Interleukin-18 promoter genotype is associated with the risk of nasopharyngeal carcinoma in Taiwan

Chung-Yu Huang,1,2 Wen-Shin Chang,3 Chia-Wen Tsai,3 Te-Chun Hsia,3 Te-Chun Shen,3,* Da-Tian Bau,3–5,* Hao-Ai Shui1,* 1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; 2Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; 3Terry Fox Cancer Research Laboratory, Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan; 4Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; 5Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan *These authors contributed equally to this work Background: The incidence rate of nasopharyngeal carcinoma (NPC) has been documented to be high in Southeast Asia. Interleukin-18 (IL-18) is a multifunctional cytokine that augments interferon-γ production and acts as an important immunomediator in the development of several types of cancer.Patients and methods: This case–control study evaluated the role of IL-18 in NPC at the DNA level by genotyping its promoter polymorphisms at positions -656, -607, and -137 in a Taiwanese population. A total of 176 patients with NPC and age- and gender-matched 352 noncancer controls were included in this study.Results: The CC genotype of the IL-18-607 polymorphism was found to be associated with significantly decreased risks of NPC compared to the AA genotype (crude OR =0.50, 95% CI =0.29–0.84, P=0.0093). This significant difference persisted even in the dominant and recessive models. A significantly lower C allele frequency at position -607 was detected in the NPC group (41.8% vs 50.3%; OR =0.77; 95% CI =0.63–1.04, P=0.0089). Regarding IL-18-656 and -137 polymorphisms, there were no differential distributions of their genotypes between the NPC and control groups. After substratification of the subjects according to their smoking, alcohol consumption, and areca chewing status, the genotype distribution of the IL-18-607 polymorphism was found to be different only among nonsmokers between the NPC and control subgroups.Conclusion: This study suggests that IL-18 plays an important role in the carcinogenesis of NPC in Taiwan and that the genotype–phenotype correlation of IL-18-607 polymorphism and its contribution to NPC need to be investigated further. Keywords: genotype, IL-18, nasopharyngeal carcinoma (NPC), polymorphism, Taiwan