Investigation Of ICAM-1 Rs5498 A>G And Rs3093030 C>T Polymorphisms With Susceptibility To Non-Small Cell Lung Cancer In A Chinese Han Population

Background and Objective: Non-small cell lung cancer(NSCLC)remains a thorny issue for global health systems.Previous studies have implicated intercellular adhesion molecule-1(ICAM-1)as a key factor in the pathogenesis of NSCLC.In addition,single nucleotide polymorphism(SNP),the most prevalent type of genetic variation in the human genome,is believed to be closely associated with lung carcinogenesis.However,the relationship between ICAM-1 gene polymorphisms and NSCLC risk has not been explored in Asian populations.In this regard,we selected two common ICAM-1 SNPs loci(rs5498 A>G and rs3093030 C>T)to assess their impact on NSCLC susceptibility,aiming to provide more valuable information on potential risk factors for NSCLC development.Methods: A total of 2,249 Chinese Han population subjects were included in this study,of which 1,193 were histologically confirmed NSCLC patients and 1,056 were healthy controls.Demographic and lifestyle characteristics were recorded,including gender,age,body mass index(BMI),smoking,and alcohol use.About 2 ml of peripheral venous blood was collected from each subject,and the extraction of genomic DNA was done with a DNA kit.The ICAM-1rs5498 A>G and rs3093030 C>T polymorphisms of all samples were assayed with the SNPscan method,and the genotype distribution of the controls was tested by Hardy-Weinberg quilibrium(HWE).Adjusted odds ratios(adjusted ORs)and their 95% confidence intervals(95% CIs)were calculated using a multivariate logistic regression model to evaluate the correlation between ICAM-1 rs5498 A>G and rs3093030 C>T variants with NSCLC risk in the overall population and each subgroup.Results: 1.The gender and age distribution between NSCLC cases and healthy controls matched well(P>0.05),but posed significant differences in smoking,drinking,and BMI(P<0.001).2.The genotype distribution of the ICAM-1 rs5498 A>G and rs3093030 C>T polymorphisms in controls met HWE,and the genotyping values of all samples were greater than 95%.3.The ICAM-1 rs5498 GG and rs3093030 TT genotypes were allied to a decreased NSCLC susceptibility(rs5498: GG vs.AA: adjusted OR=0.64,P=0.013;GG vs.AA/GA.adjusted OR=0.63,P=0.009;rs3093030: TT vs.CC: adjusted OR=0.63,P=0.042;TT vs.CC/CT:adjusted OR=0.60,P=0.026).4.Stratified analysis suggested that:(1)the ICAM-1 rs5498 GG genotype endowed with a reduced NSCLC risk to the male,age<59,non-smoking,non-drinking,and BMI<24 subgroups;(2)the ICAM-1 rs3093030 TT genotype was observed to decrease the NSCLC risk in the male,non-smoking,and non-drinking subgroups;(3)the ICAM-1 rs3093030 CT genotype was a protective factor for NSCLC in the drinking subgroup but a risk factor for NSCLC in the non-drinking subgroup.Conclusions: In summary,our study reveals that the ICAM-1 rs5498 A>G and rs3093030 C>T polymorphisms serve as protective factors for NSCLC in Chinese Han populations.More welldesigned case-control studies should be conducted to further validate our results.