APOBEC3B Deletion Polymorphism And Lung Cancer Risk In The Southern Chinese Population

Background and Objective Approximately 80–85% of lung cancer is the non-small cell lung cancer(NSCLC)subtype,which ranks as the leading cause of cancer deaths worldwide.APOBEC3B(A3B)was reported to be a key source of mutations in NSCLC.However,the role of the A3B deletion polymorphism in the etiology of NSCLC has not been well-documented.MethodsA case-control study with 317 NSCLC patients and 334 healthy controls was conducted to explore the association between the A3B deletion polymorphism and the risk of NSCLC.The unconditional logistic regression model was performed to calculate the odds ratio(OR)and the95% confidence interval(CI),and the confounding factors were adjusted,including age,gender,and smoking status,to estimate the risk.An analysis of gene-environment interactions was performed using multifactor dimensionality reduction(MDR)software.Results1.We found that there are statistical differences in age,gender,smoking and genotype distribution between the case group and the control group(P<0.05).2.After adjusting for confounding factors,we found that there is a significant association between APOBEC3A＿B deletion and NSCLC risk.The risk of NSCLC in individuals with the deletion type is 2.71 times that of individuals with the wildtype.3.In the interaction analysis,it was found that in NSCLC,compared with the reference group(wild type,female and non-smoker),individuals with heterozygous,female and non-smokers have a lower risk of NSCLC,regardless of Whether or not they smoke,men have a higher risk of NSCLC.Among individuals carrying heterozygous forms,non-smokers and smokers have 1.91 times and 3.38 times the risk of NSCLC,respectively.Smokers have a higher risk of NSCLC.Among individuals carrying the missing form,the risk of NSCLC in non-smokers increased by7.31 times,and the risk of NSCLC in smokers was up to 7.77 times.4.The expression of APOBEC3B in lung cancer tissue is higher than that in normal lung tissue,and the difference is statistically significant(P<0.01);in the lung cancer tissue group,the expression of wild-type is higher than that of the deletion type,and the difference is statistically significant(P<0.01));The expression of APOBEC3 A in lung cancer tissues was higher than that in adjacent tissues and normal tissues,but there was no statistical difference.5.12 h after transfection of g APOBEC3B plasmid to A549 cells,we found that the proportion of cells in the dormant phase and pre-division phase(G0-G1 phase)of the g APOBEC3B plasmid group was lower than that of the control p LKO.1 empty plasmid group and blank control group(P<0.0001),the proportion of cells in the late stage of DNA synthesis and division(G2-M phase)and DNA synthesis phase(S phase)increased significantly(P<0.01).ConclusionsWe propose that the A3B deletion polymorphism can increase the risk of developing NSCLC,and their interactions with gender and smoking may contribute to the risk of NSCLC in the southern Chinese population.