title: Genetic variant in the 3'-untranslated region of VEGFR1 gene influences chronic obstructive pulmonary disease and lung cancer development in Chinese population.
abstract: Lung inflammation and epithelial to mesenchymal transition (EMT) are two pathogenic features for the two contextual diseases: chronic obstructive pulmonary disease (COPD) and lung cancer. VEGFR1 (or FLT1) plays a certain role in promoting tumour growth, inflammation and EMT. To simultaneously test the association between the single nucleotide polymorphisms (SNPs) in VEGFR1 and risk of COPD and lung cancer would reveal genetic mechanisms shared by these two diseases and joint aetiology. We conducted a two-population hospital-based case-control study. Three potential functional SNPs (rs664393, rs7326277 and rs9554314) were genotyped in southern Chinese and validated in eastern Chinese to explore their associations with COPD risk in 1511 COPD patients and 1677 normal lung function controls, and with lung cancer risk in 1559 lung cancer cases and 1679 cancer-free controls. We also detected the function of the promising SNP. Individuals carrying the rs7326277C (CT+CC) variant genotypes of VEGFR1 had a significant decrease in risk of both COPD (OR = 0.78; 95% CI = 0.68-0.90) and lung cancer (OR = 0.79; 95% CI = 0.64-0.98), compared with those carrying the rs7326277TT genotype. Functional assays further showed that the rs7326277C genotypes had lower transcriptional activity and caused decreased VEGFR expression, compared with the rs7326277TT genotype. However, no significant association was observed for the other two SNPs (rs664393 and rs9554314) and either COPD or lung cancer risk. Our data suggested that the rs7326277C variant of VEGFR1 could reduce both COPD and lung cancer risk by lowering VEGFR1 mRNA expression; the SNP might be a common susceptible locus for both COPD and lung cancer.
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 510182, Guangdong, China, School of Public Health, Guangdong Key Laboratory of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou 510310, Guangdong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 510182, Guangdong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou 215123, China and.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Deng
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 510182, Guangdong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 510182, Guangdong, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Yang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 510182, Guangdong, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Yang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 510182, Guangdong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 510182, Guangdong, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Fang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 510182, Guangdong, China.
authors.forename: Fuman
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510120, Guangdong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510120, Guangdong, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Ji
authors.affiliation: Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510120, Guangdong, China.
authors.forename: Pixin
authors.initials: P
authors.lastname: Ran
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou 215123, China and.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 510182, Guangdong, China, jcLu@gzhmc.edu.cn.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1