Association Of BTLA Polymorphisms With Susceptibility To Non-Small-Cell Lung Cancer

Background and Purpose:Lung cancer（LC）is the most common malignancy,and its pathogenesis is very complex and still unclear.Current studies suggest that it may be the cause of the progression of cancer and other related diseases in the interaction between environmental factors and genetic variation.Studies have shown that the occurrence and development of tumors are closely related to immunity.B and T lymphocyte attenuator（BTLA）is one of the most studied targets of LC immunotherapy.It has been reported that BTLA SNPs are associated with the risk of various cancers,however,the susceptibility of BTLA to NSCLC remains unclear.We conducted the study design to clarify the relationship between BTLA locus variants and the risk of NSCLC.Methods:A total of 1,904 volunteers was recruited,including 1,003 LC patients and901 healthy people as controls.Significant mutation sites were selected from the gene variation database and four candidate BTLA polymorphisms（BTLA rs1982809G>A,rs16859629T>C,rs2171513G>A,rs3112270A>G）were genotyped using SNP_SCAN^TMgenotyping technology.Statistical methods and software were used for data collection and analysis.Logistic regression model was constructed to calculate the risk ratio between each candidate gene polymorphism locus and NSCLC susceptibility,and a P value less than 0.05 was considered to be statistically significant.Results:In this study,we found:In the whole,1.BTLA rs3112270A>G gene polymorphism may reduce the risk of NSCLC susceptibility（GG+AG vs.AA OR=0.83,95%CI=0.69-0.99,P=0.038）.After adjusting the interference of confounding factors,the logistic regression analysis model was established.The results showed that BTLA rs3112270A>G locus polymorphism was not associated with NSCLC susceptibility.2.BTLA rs1982809G>A gene polymorphism may decrease the risk of NSCLC（GA vs.GG OR=0.81,95%CI=0.67-0.98,P=0.030;AA+GA vs.GG OR=0.83,95%CI=0.69-0.99,P=0.042）.Logistic regression analysis was established by adjusting the included risk factors,BTLA rs1982809G>A polymorphism at this locus was still associated with NSCLC susceptibility（GA vs.GG adjusted OR=0.81,95%CI=0.66-0.99,P=0.043）.In the stratified analysis,1.After adjusting the interference of confounding factors,the results showed that BTLA rs16859629T>C locus polymorphism may increase the risk of squamous cell carcinoma（CC vs.TT adjusted OR=9.85,95%CI=1.37-71.03,P=0.023;CC vs.TT+TC adjusted OR=9.55,95%CI=1.32-68.66,P=0.025）.2.BTLA rs1982809G>A gene polymorphism decreased the risk of non-squamous cell carcinoma（GA vs.GG OR=0.79,95%CI=0.65-0.97,P=0.022;AA+GA vs.GG OR=0.81,95%CI=0.67-0.98,P=0.026）.Logistic regression analysis was performed after adjusting for included risk factors（age,sex,alcohol consumption,smoking status,BMI）and the BTLA rs1982809G>A locus polymorphism was still associated with NSCC susceptibility（GA vs.GG adjusted OR=0.79,95%CI=0.64-0.97,P=0.026;AA+GA vs.GG adjusted OR=0.81,95%CI=0.66-0.99,P=0.037）.3.BTLA rs1982809G>A SNP may reduce the susceptibility to NSCLC risk in the age≥59 years old,never drink,BMI≥24kg/m² people（Age≥59 years old:GA vs.GG adjusted OR=0.75,95%CI=0.57-0.98,P=0.036;non-drinking group:GA vs.GG adjusted OR=0.76,95%CI=0.61-0.94,P=0.013;AA+GA vs.GG adjusted OR=0.77,95%CI=0.63-0.95,P=0.016;BMI≥24kg/m²:GA vs.GG adjusted OR=0.69,95%CI=0.50-0.97,P=0.030;AA+GA vs.GG adjusted OR=0.72,95%CI=0.53-0.99,P=0.041）.In haplotype analysis,the results show that:BTLA haploid type T_rs16859629A_rs1982809G_rs2171513G_rs3112270 can significantly change the susceptibility of NSCLC.Conclusions:Based on the above results,the results of this study suggest that BTLA rs1982809 and rs16859629 polymorphisms may affect NSCLC susceptibility in the Chinese population.Due to the limitations of samples and research centers,it is necessary to recruit larger samples and carry out multi-center cooperation in the future to further verify those conclusions.