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Background  The purpose of this study was to identify gene polymorphisms of interleukin-18 (IL-18)  -607A/C  and  -137G/C  specific to patients with oral cancer susceptibility and clinicopathological status.Methodology and Principal Findings  A total of 1,126 participants, including 559 healthy people and 567 patients with oral cancer, were recruited for this study. Allelic discrimination of   -607A/C   (rs1946518) and   -137G/C   (rs187238) polymorphisms of the  IL-18   gene  was assessed by a real-time PCR with the TaqMan assay. There was no significant association between  IL-18  -607A/C   polymorphism and oral cancer risk. However, among alcohol consumers, people with  A/A   homozygotes  of  IL-18  -607A/C   polymorphism had a 2.38-fold (95% CI=1.17-4.86; p=0.01) increased risk of developing oral cancer compared with those with  C/C   homozygotes . The participants with  G/C   heterozygotes  of  IL-18 -137   polymorphism  had a 1.64-fold (95% CI: 1.08-2.48; p=0.02) increased risk of developing oral cancer compared with those with  G/G  wild type homozygotes. Both sets of statistics were determined after adjusting for confounding factors. Among people who had exposure to oral cancer-related environmental risk factors such as areca, alcohol, and tobacco consumption, the adjusted odd ratios and 95% confidence intervals were increased to a 2.02-fold (95% CI=1.01-4.04; p=0.04), 4.04 (95% CI=1.65-9.87; p=0.002) and a 1.66-fold (95% CI=1.00-2.84; p=0.05) risk of developing oral cancer. However, patients with  G/C  alleles of  IL-18 -137  were correlated with a lower clinical stage (AOR=0.59; 95% CI=0.39-0.89; p=0.01), smaller tumor size (AOR=0.56; 95% CI=0.35-0.87; p=0.01), and non-lymph node metastasis (AOR=0.51; 95% CI=0.32-0.80; p=0.003).Conclusion    IL-18 -137   G/C  gene polymorphism may be a factor that increases the susceptibility to oral cancer, as well as a protective factor for oral cancer progression. The interactions of gene to oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.

Impact of Interleukin-18 Polymorphisms -607A/C and -137G/C on Oral Cancer Occurrence and Clinical Progression