The Association Between Interleukin-18 Single Nucleotide Polymorphisms And The Susceptibility Of Laryngeal Carcinoma

Background:Laryngeal neoplasm is one of the most common malignant tumors in the head and neck,accounting for 1-5%of all human malignant tumors.According to the latest statistics of the American Cancer Association,177422 new cases of laryngeal cancer and 94771 deaths occurred in the world in 2018.The etiology of laryngeal cancer is still unclear.Epidemiological data confirm that it is related to smoking,drinking,radiation,sexual hormone metabolism disorder and other factors,which is the result of synergistic effect of various carcinogenic factors.With the development of genome wide association study(GWAS)in recently years,the role of genetic factors in the pathogenesis of laryngeal cancer has attracted much attention,especially the s ingle nucleotide polymorphism(SNP)of multiple genes is closely related to the occurrence,development,metastasis and prognosis of laryngeal cancer.Growing evidence demonstrated that IL-18-137G/C and-607C/A gene polymorphisms are associated with the susceptibilities of several other types of cancers.However,the single nucleotide polymorphisms of these two promoter sites and the susceptibility of laryngeal cancer have not been reported in the literature.Objective:The aim of this study is to identify the association between IL-18-137G/C and-607C/A gene polymorphisms and the susceptibilities of laryngeal squamous cell carcinoma(LSCC)in a C hinese Han population in Shandong Province.Methods:A case-control study was used to this study,the subjects were selected from the Han population in Shandong Province.This study randomly selected people who visited Linyi people’s Hospital from May 2017 to October 2019,a total of 73 LSCC patients(70males and 3 females)as case group and 73 healthy individuals(70 males and 3 females)as control group,all participants signed the informed consent form.C linical information(age,smoking history,drinking history,etc.)and peripheral blood samples(2ml)were collected,then the whole blood DNA were extracted by DNA extraction kit of Tiangen biochemical magnetic beads and genotyping was performed by sanger sequencing method.The chi-square goodness of fit test was used to analyze whether the control group was in accordance with Hardy Weinberg equilibrium law.The q uantitative data in the case group and the control group were analyzed by the student’s-t test,and the qualitative data were analyzed by Pearson?~2test or Fisher exact test.The association between the two single nucleotide polymorphisms(SNPs)and the risk of LSCC were calculated by logistic regression analysis.Results:Our results showed there was no significant difference in age and gender distribution between the case group and the control group(P>0.05).The proportion of smokers and drinkers in the case group was 80.8%and 68.5%respectively,while that in the healthy control group was 42.5%and 41.1%respectively.The comparison between the two groups showed that the proportion of smokers and drinkers in the laryngeal cancer group was significantly higher than that in the healthy control group(P<0.001).Chi square goodness of fit test showed that the two SNP loci in the control group were in line with Hardy Weinberg’s genetic law.The risk of LSCC increased significantly in both smokers and drinkers(O R=5.710,P=0.000;OR=3.116,P=0.001).The risk of LSCC in GC carriers with variant genotype was higher(adjusted OR=2.968,P=0.014)in loci-137G/C.There was no significant correlation between il-18-607C/A polymorphism and LSCC(P>0.05).Stratified analysis of-137G/C loci showed that compared with wild GG genotypes,those with GC genotypes with age≤65(P=0.019),non-smoking(P=0.038)and non drinking(P=0.025)had an increased risk of laryngeal cancer,and the corresponding risk was increased by about 7.6 times,3.6 times and 3.7 times,respectively.The difference was statistically significant.Conclusion:Our findings suggest that IL-18 promoter-137G/C but not-607C/A polymorphism variants are associated with higher risk in LSCC,the association between IL-18-137G/C polymorphism and the susceptibility to LSCC might only occur in non-smokers and non-drinkers.