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

Abstract

BackgroundThe 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 FindingsA 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.

Combinations of SERPINB5 gene polymorphisms and environmental factors are associated with oral cancer risks

“…It was reported that genetic factors play important roles in oral cancer susceptibility, and discovery of potential oral cancer-related SNPs was recommended for the early detection of possible candidates for oral cancer development [9, 13–15]. SERPINB5 was reported to be a tumor suppressor by inducing apoptosis and inhibiting proliferation, invasion, and migration of tumor cells [19, 20].…”

“…The final volume for each reaction was 10 μL and contained 5 μL of the TaqMan Universal PCR Master Mix, 0.25 μL of the primer/TaqMan probe mix, and 10 ng of genomic DNA. The real-time PCR consisted of an initial denaturation step at 95°C for 10 min followed by 40 cycles consisting of 92°C for 15 s and 60°C for 1 min [15, 17, 18]. The research assistant who conducted the laboratory analyses was blinded to the participants’ diagnoses.…”

“…Single-nucleotide polymorphisms (SNPs) are reported to be important factors in oral cancer susceptibility [9, 13–15]. The SERPINB5 gene is located on chromosome 18q21.3, and expression of the SERPINB5 gene can be modulated by regulating the initiation of transcription on the promoter region in human oral cancer cell lines [16].…”

Interleukin-18 Gene Polymorphism and Some Risk Factors in Iraqi Patients With Breast Cancer

“…The alteration from the "C allele to the "A" allele at site −607C/A and at site −137 G/C alternation from the G allele to the C allele in the (promoter area) were prophesied to be the molecular factor linking sites for the cyclic adenosine monophosphate responsive element between protein and H4TF-1 factor, respectively in addition, polymorphisms of the two positions have been correlated with the activity of IL-18 gene promoter transcription, which can impact the IL-18 expression and, may be, of IFN-γ; these changes in alleles, potentially be the essential mechanism of IL-18 involvement in different diseases [23,24]. IL-18 polymorphism has been shown correlated with different diseases such as oral cancer [10], colorectal cancer [11], thyroid cancer [12], bladder cancer [13], lung cancer [14], and nasopharyngeal carcinoma" [15].…”

“…Three types of SNPs of the IL-18 gene in the promoter nucleotides was determined, called −137 G/C (rs187238), −656 G/T or rs1946518, and −607 C/A or rs1946519 [9]. IL-18 gene polymorphisms have shown correlation with different diseases such as oral cancer [10], colorectal cancer [11], thyroid cancer [12], bladder cancer [13], lung cancer [14]. and nasopharyngeal carcinoma [15].…”