Association Of TNFSF15 Genetic Variants With The Risk Of Lung Cancer

Objectives This study was used to explore the relationship between the genetic variants of TNFSF15 gene promoter region and the susceptibility of lung cancer,and to analysis the effect of TNFSF15 expression on the prognosis of lung cancer patients,which can provide for the relevant theoretical basis and the prognosis of patients with lung cancer screening.Methods A case-control study was used to select the patients in Tangshan,Hebei Province with small cell lung cancer and non-small cell lung cancer case group(209 cases,340 cases)and control group(460 cases),using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)to genotype the genetic variation in the TNFSF15 promoter region.Unconditional Logistic regression model was used to calculate the OR value and 95% confidence interval(95% CI)for each genotype affecting the risk of lung cancer;stratified analysis was used to further investigate the effects of gender,age,and smoking status on the risk of lung cancer analysis.TCGA data was used to compare the differences in TNFSF15 expression between lung adenocarcinoma/squamous cell carcinoma and normal lung tissue.Kaplan-Meier analysis and Log-rank test were used for survival analysis.Results 1 According to epidemiological statistics and bioinformatics analysis,the genetic variation in the promoter region of TNFSF15 gene was screened out:rs7848647 T>C and rs6478109 A>G.In the TNFSF15 rs7848647 T>C mutation,compared with the TT genotype carriers,the CC genotype carrier had a significantly higher risk of developing small cell lung cancer(OR = 1.81,95% CI = 1.11 ~ 2.95,P = 0.017).Gender stratification showed: compared with TT genotype carriers,CC genotype male carriers can increase the risk of developing small cell lung cancer(OR = 1.92,95% CI = 1.08 ~ 3.39,P = 0.026),The risk in the female small cell lung cancer patient was not affected(OR = 1.92,95% CI = 0.72 ~ 5.12,P = 0.194);Age stratification showed that no genetic variant of rs7848647 was associated with the risk of small cell lung cancer in the low age group(OR = 1.42,95% CI = 0.76 ~ 2.65,P = 0.270),while CC genotype carrier was found to be associated with the risk of small cell lung cancer in the high age group(OR = 2.38,95% CI = 1.06 ~ 5.33,P = 0.035).Stratified analysis of smoking status showed that no rs7848647 mutation was found to affect the risk of small cell lung cancer,the OR and 95% CI were 1.97(0.95 ~ 4.08)and 1.73(0.88 ~ 3.40)in non-smokers and smokers,respectively.Further stratified analysis of the severity of smoking also found no impact of rs7848647 mutation on the risk of small cell lung cancer,and the OR and 95% CI in the mild smoking and severe smoking population were 1.59(0.58 ~ 4.37)and 1.66(0.65 ~ 4.22).2 For the rs6478109 A>G genetic variation,compared with the AA genotype carriers,the risk of small cell lung cancer was significantly higher in carriers of the GG genotype(OR = 2.18,95% CI = 1.31 ~ 3.63,P = 0.003).Gender stratification showed that compared with rs6478109 AA genotype carriers,women with GG genotype increased the risk of developing small cell lung cancer(OR = 7.93,95% CI = 2.11 ~ 29.77,P = 0.002),while males were not affected(OR = 1.49,95% CI = 0.84 ~ 2.66,P = 0.177);Age stratified showed that association between rs6478109 genetic variation and risk of small cell lung cancer was found in GG genotype carrier in low age group(OR = 2.96,95% CI = 1.49 ~ 5.88,P = 0.002);no association between GG genotype carriers and the risk of small cell lung cancer(OR = 1.46,95% CI = 0.67 ~ 3.18,P = 0.347).Stratified analysis of smoking status showed that GG gene carriers were associated with the risk of small cell lung cancer in smoking population(OR = 2.63,95% CI = 1.23 ~ 5.60,P = 0.012);but no rs6478109 was found in nonsmoking population.The mutation affected the susceptibility of small cell lung cancer(OR = 1.72,95% CI = 0.84 ~ 3.53,P = 0.136).Further stratified by the severity of smoking,we found the GG genotype in mild smokers affect the risk of small cell lung cancer(OR = 3.42,95% CI = 1.03 ~ 11.41,P = 0.046),while we found no correlation in heavy smokers(OR = 2.30,95% CI = 0.82 ~ 6.42,P = 0.113).3 There was no statistical difference between the distribution of TNFSF15 rs7848647 T>C and rs6478109 A>G in the nonsmall cell lung cancer case group and the control group(P>0.05).4 The TCGA database analysis showed that the expression of TNFSF15 in lung squamous cell carcinoma was 2.475 times lower than that in normal lung tissue(P = 0.001),while there was no difference in lung adenocarcinoma(P = 0.116).Further analysis of the prognosis of patients with non-small cell lung cancer revealed that the 5-year survival rate was 54.8%(95% CI = 0.47 ~ 0.64,P = 0.042)in patients with low TNFSF15 expressing squamous cell carcinoma,which was significantly higher than that of TNFSF15 expressing lung In the squamous cell carcinoma group(P = 0.048),the 5-year survival rate was 42.3%(95% CI = 0.35 ~ 0.51,P = 0.041).The 5-year survival rate of the lung adenocarcinoma group was not related to the level of TNFSF15 expression(P > 0.05).Conclusions Genetic variation of rs7848647 T>C and rs6478109 A>G in the promoter region of TNFSF15 affects the risk of small cell lung cancer.At the same time,the expression of TNFSF15 is closely related to the prognosis of non-small cell lung squamous cancer.