title: Association of the VEGF 936C>T polymorphism with FDG uptake, clinical, histopathological, and metabolic response in patients with adenocarcinomas of the esophagogastric junction.
abstract: OBJECTIVE
  The MUNICON trial confirmed prospectively the usefulness of early response evaluation by 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) . Metabolic responders (R) showed initially a higher FDG uptake compared with nonresponders (p = 0.018). An association of the vascular endothelial growth factor (VEGF) 936C>T polymorphism and FDG uptake was reported for breast cancer. Therefore, we investigated the VEGF 936C>T polymorphism for an association with response and survival.
  
  
  METHODS
  The study was based on 110 patients included in the MUNCON trial (103 male, seven female; 75 AEG I, 35 AEG II, event-free survival (EFS) median 21.1 ± 4.6 months). Response was significantly associated with EFS. The VEGF 936C>T polymorphism was determined by PCR and restriction fragment length polymorphism analysis. For analysis, the T-variants were combined.
  
  
  RESULTS
  One hundred two patients were evaluable. Seventy-two patients showed the CC, 24 the CT, and six the TT genotype. Median EFS was 29.3 months for CC and 11.7 months for CT/TT (p = 0.04). No association of the genotypes (CC or CT/TT) with the SUV or response was found. Multivariate analysis revealed histopathological regression (p = 0.003) and genotype (p = 0.04) as independent prognostic factors. A combination of genotype and PET response (Gen-PET) defines three prognostic groups early in the course of treatment (p = 0.002). Cox regression analysis including clinical and histopathological response and Gen-PET reveals Gen-PET as independent prognostic factor (p = 0.003).
  
  
  CONCLUSIONS
  The VEGF 936C>T polymorphism is a prognostic factor in patients undergoing neoadjuvant chemotherapy, although it is not associated with FDG uptake and response. The combination of metabolic response and VEGF 936C>T polymorphism defines three different prognostic groups. These findings need to be confirmed prospectively. This study has been registered in the European Clinical Trials Database as trial 2007-003356-11.
authors.affiliation: National Center of Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lorenzen
authors.forename: Ben
authors.initials: B
authors.lastname: Panzram
authors.forename: Gisela
authors.initials: G
authors.lastname: Keller
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
authors.forename: Karin
authors.initials: K
authors.lastname: Becker
authors.forename: Ruppert
authors.initials: R
authors.lastname: Langer
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Jorg Rudiger
authors.initials: JR
authors.lastname: Siewert
authors.forename: Katja
authors.initials: K
authors.lastname: Ott
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D017931:DNA Primers; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006801:Humans; D011110:Polymorphism, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18
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