title: VEGF polymorphisms in early cervical cancer susceptibility, angiogenesis, and survival.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) plays an important role in cervical carcinogenesis. We hypothesized that VEGF genetic polymorphisms may affect cancer susceptibility, angiogenesis, and survival in patients with early cervical cancer.
  
  
  METHODS
  Among 215 healthy subjects and 199 early cervical cancer patients who were treated with surgical resection, we specifically investigated four genetic polymorphisms within the VEGF gene (-2578C>A, -460 T>C, +405G>C, and +936C>T). VEGF and CD31 microvessel density (MVD) were measured using tissue microarrays constructed from 117 patients who had available tissue.
  
  
  RESULTS
  Risk of cervical cancer was decreased in subjects with the VEGF -2578A/A genotype (adjusted OR=0.39, 95% CI 0.16-0.96). Angiogenesis measured by CD31 MVD was significantly decreased in patients with the VEGF +405C/C genotype and VEGF -2578C - -460 T - +405C haplotype (recessive model; adjusted OR=0.32, 95% CI 0.11-0.99, equally). Moreover, VEGF +405C/C and VEGF -2578C - -460 T - +405C haplotype were significantly related to shorter disease-free survival (adjusted HR=3.18, 95% CI 1.13-8.94, equally) and overall survival (adjusted HR=8.86, 95% CI 1.40-56.08, equally) by multiple Cox regression analysis.
  
  
  CONCLUSIONS
  Polymorphisms of VEGF genes may affect cancer susceptibility and survival of early cervical cancer by modulating tumor angiogenesis. Prospective study among homogeneously treated patients is warranted.
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yun Hwan
authors.initials: YH
authors.lastname: Kim
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.forename: In-Ae
authors.initials: IA
authors.lastname: Park
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Jae Weon
authors.initials: JW
authors.lastname: Kim
authors.forename: Seung Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: Noh-Hyun
authors.initials: NH
authors.lastname: Park
authors.forename: Yong-Sang
authors.initials: YS
authors.lastname: Song
authors.forename: Soon-Beom
authors.initials: SB
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A