title: The Different Effect of VEGF Polymorphisms on the Prognosis of Non-Small Cell Lung Cancer according to Tumor Histology.
abstract: Vascular endothelial growth factor (VEGF) contributes to tumor angiogenesis. The role of VEGF single nucleotide polymorphisms (SNPs) in lung cancer susceptibility and its prognosis remains inconclusive and controversial. This study was performed to investigate whether VEGF polymorphisms affect survival outcomes of patients with early stage non-small cell lung cancer (NSCLC) after surgery. Three potentially functional VEGF SNPs (rs833061T>C, rs2010963G>C, and rs3025039C>T) were genotyped. A total of 782 NSCLC patients who were treated with surgical resection were enrolled. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. In overall population, none of the three polymorphisms were significantly associated with OS or DFS. However, when the patients were stratified by tumor histology, squamous cell carcinoma (SCC) and adenocarcinoma (AC) had significantly different OS (Adjusted hazard ratio [aHR] = 0.76, 95% CI = 0.56-1.03 in SCC; aHR = 1.33, 95% CI = 0.98-1.82 in AC; P for heterogeneity = 0.01) and DFS (aHR = 0.75, 95% CI = 0.58-0.97 in SCC; aHR = 1.26, 95% CI = 1.00-1.60 in AC; P for heterogeneity = 0.004) according to the rs833061T>C genotypes. Our results suggest that the prognostic role of VEGF rs833061T>C may differ depending on tumor histology.
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Soyeon
authors.identifier: http://orcid.org/0000-0002-1868-7715
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.|Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Hyo Gyoung
authors.identifier: http://orcid.org/0000-0003-0600-227X
authors.initials: HG
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.|Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Jin Eun
authors.identifier: http://orcid.org/0000-0001-7833-2257
authors.initials: JE
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Jang Hyuck
authors.identifier: http://orcid.org/0000-0001-5537-3013
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Hyo Jung
authors.identifier: http://orcid.org/0000-0002-0011-2542
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Sun Ah
authors.identifier: http://orcid.org/0000-0002-8088-9764
authors.initials: SA
authors.lastname: Baek
authors.affiliation: Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Eungbae
authors.identifier: http://orcid.org/0000-0002-1727-5380
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Yangki
authors.identifier: http://orcid.org/0000-0001-8212-109X
authors.initials: Y
authors.lastname: Seok
authors.affiliation: Department of Biostatistics Center, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Won Kee
authors.identifier: http://orcid.org/0000-0003-4217-5792
authors.initials: WK
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Korea.
authors.forename: Shin Yup
authors.identifier: http://orcid.org/0000-0002-2121-7335
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Korea.
authors.forename: Seung Soo
authors.identifier: http://orcid.org/0000-0002-7309-9254
authors.initials: SS
authors.lastname: Yoo
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Jaehee
authors.identifier: http://orcid.org/0000-0001-8111-7320
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Seung Ick
authors.identifier: http://orcid.org/0000-0002-7246-0909
authors.initials: SI
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Chang Ho
authors.identifier: http://orcid.org/0000-0002-1550-5752
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Korea.
authors.forename: Sukki
authors.identifier: http://orcid.org/0000-0002-9309-8865
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.|Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Korea. jaeyong@knu.ac.kr.
authors.forename: Jae Yong
authors.identifier: http://orcid.org/0000-0001-7993-4495
authors.initials: JY
authors.lastname: Park
mesh_terms: D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Histology; Non-Small Cell Lung Cancer; Polymorphisms; Survival