The Relationship Between CDH1,FANCB And APC Gene Polymorphisms And Lung Cancer Susceptibility And The Expression And Function Of FANCB In Lung Adenocarcinoma

【Background and Objective】: lung cancer is the main cause of cancer-related death [1],and non-small cell lung cancer(NSCLC)is the main type,accounting for about 85% of lung cancer.NSCLC includes adenocarcinoma(ADC),squamous cell carcinoma(SCC),large cell lung cancer,etc.[2].Studies on the etiology of lung cancer have confirmed that smoking,second-hand smoke,cannabis,occupational contact,history of non-infectious respiratory diseases,and genetic genes are closely related to the occurrence of lung cancer [3].Among them,genetics is an important reason that we cannot ignore.A single nucleotide polymorphism(SNP),the most common type of genetic variation,is a polymorphism in a DNA sequence caused by a variation in a single nucleotide.SNPS can lead to differences in individual susceptibility to lung cancer and clinicopathologic features of lung cancer,but the mechanism is still not understood.This study aims to investigate the relationship between SNP of CDH1,FANCB and APC genes and genetic susceptibility to lung cancer.At the same time,after concluding that the rs754552650 site of FANCB gene can significantly reduce the incidence of lung adenocarcinoma,we consulted relevant literature and found that this gene has been widely reported in Fanconi anemia,but no relevant literature has been reported in lung cancer.Therefore,we further studied the relationship between FANCB gene and lung adenocarcinoma.【Method】: A case-control study was carried out to collect 270 cases of lung cancer from the Department of Lung Cancer Surgery,Tianjin Medical University General Hospital.Meanwhile,blood samples from 445 healthy volunteers were collected as controls.Genomic DNA was extracted and genotyping was performed using Taqman? SNP genotyping kit.The distribution of SNPs loci of CDH1 gene rs201141645,FANCB gene rs754552650 and APC gene rs149353082 in Chinese population was analyzed.To explore the relationship between different genotypes and the risk of lung cancer,Chi-square test and Logistic regression analysis were used.Bioinformatics and lung adenocarcinoma cell lines PC9 and H1975 were used for follow-up in vitro experiments.After FANCB expression was knocked down by si RNA transfection technology and confirmed by RT-q PCR,the growth ability of lung adenocarcinoma cells after FANCB knockdown was measured by cck8,Edu and colony formation experiments.At the same time,Transwell assay was used to detect the effect of FANCB knockdown on the migration and invasion ability of lung adenocarcinoma cells.【Results】: The distribution frequencies of AA,A/G and GG genotypes at rs754552650 of FANCB gene were 27.2%,52.6% and 20.2% in the control group,respectively.The distribution frequencies of AA and A/G genotypes were 93.7% and 6.3%,respectively.GG genotype was not detected in the case group.The A/G genotype of rs754552650 of FANCB gene was significantly different between the case and control groups.Carriers had a significantly reduced risk of lung cancer(OR=0.035,95%CI: 0.020-0.062,P<0.001).The CDH1 gene rs201141645 A/C and CC genotypes were only present in the control group.In addition,only one sample in the case group was found to have APC gene rs149353082 C/G genotype.We downloaded the unified and standardized pan-cancer data set from the TCGA database,and further extracted the expression data of FANCB gene in each sample.It was found that FANCB gene was highly expressed in both lung adenocarcinoma and lung squamous cell carcinoma,which increased the risk of death in lung adenocarcinoma(OR=1.17,95%CI: 1.03-1.32,P<0.01),survival analysis showed that patients with lung adenocarcinoma with high FANCB expression had poor prognosis(OR=1.66,95%CI:1.26-2.19,P=0.00025).The results of cck8,Edu,colony formation and Transwell experiments in vitro showed that the proliferation and invasion ability of lung adenocarcinoma cell lines(PC9,H1975)were significantly reduced after FANCB gene knockdown.【Conclusions】: In the Chinese population,FANCB gene rs754552650 A/G genotype carriers have a significantly reduced risk of lung adenocarcinoma,and FANCB gene promotes the occurrence and development of lung adenocarcinoma.