Study On The Relationship Between RBFOX1 Polymorphism And Lung Cancer Susceptibility In Non-smoking Women

Objective: Cancer,as one of the most serious chronic diseases with the highest morbidity and mortality,is a serious threat to human health.Lung cancer is one of the most common cancers and has become a major public health threat in the world.The burden of lung cancer is also severe in China.Currently,smoking is generally considered to be the main risk factor for lung cancer.However,in addition to tobacco exposure,other factors,such as the genetic factor,also play an indispensable role.Studies have shown that RBFOX1 gene may affect the development and prognosis of tumors.Therefore,the purpose of this study was to investigate the association between single-nucleotide polymorphisms(SNPs: rs4787050 and rs8045980)in RBFOX1 and lung cancer susceptibility in non-smoking women in the northeast of China,and to analyze the interaction between the two SNPs and cooking oil fume exposure on lung cancer risk.Methods: All subjects in this study were non-smoking women in northeast China(647patients with lung cancer and 675 cancer-free control subjects).Five milliliters of venous blood was collected from each subject and retained.The genomic DNA of anticoagulant blood was extracted by the classical phenol-chloroform method.Then,rs4787050 and rs8045980 were genotyped by Taqman? real-time PCR.All statistical analyses were conducted by SPSS software(version 22.0)with two-sided test,and P ≤ 0.05 as the criterion of statistical significance.Chi-square test and t-test(or non-parametric test)were used to evaluate the distribution of categorical and continuous variables in lung cancer patients and the control group,respectively.Unconditional logistic regression analysis was used to calculate odds ratios(ORs)and 95% confident intervals(CIs).The crossover analysis was used to evaluate the interaction between the two SNPs and cooking oil fume exposure.Additive and multiplicative models were used to further analyze the interaction between the two SNPs and cooking oil fume exposure.Results: The results of this study indicated a significant correlation between RBFOX1(rs4787050 and rs8045980)SNPs and lung cancer susceptibility.In the homozygous mutation model of rs4787050,taking individuals with AA genotype as the reference,the risk of lung cancer was significantly increased in individuals with GG genotype(adjusted OR = 2.471,95%CI = 1.262-4.836,P = 0.008).In the homozygous mutation model of rs8045980,the risk of lung cancer in individuals with AA genotype was 1.629 times higher than that in individuals with CC genotype(adjusted OR = 1.629,95%CI =1.125-2.357,P = 0.010).Further stratification analyses revealed that rs4787050 polymorphism was associated with the risk of lung adenocarcinoma and small cell lung cancer,while rs8045980 polymorphism was only associated with the risk of lung adenocarcinoma.The polymorphism of rs4787050 was associated with the risk of lung cancer only in subjects who were less than or equal to 60 years old,while the polymorphism of rs8045980 was associated with the risk of lung cancer in subjects who were less than or equal to 60 years old,or greater than 60 years old.The results of the linkage disequilibrium analysis showed that there was no strong linkage disequilibrium between rs4787050 and rs8045980.In addition,this study found that exposure to cooking oil fume increased the risk of lung cancer.However,no interaction between rs4787050 and rs8045980 SNPs and cooking oil fume exposure to lung cancer susceptibility was found.Conclusions: The results of this study suggested that RBFOX1 rs4787050 and rs8045980 SNPs are associated with the risk of lung cancer,and the two SNPs may be new biomarkers for lung cancer susceptibility.