title: Heme oxygenase-1 promoter polymorphism is a predictor of disease relapse in pancreatic neuroendocrine tumors.
abstract: BACKGROUND
  Current available preoperative diagnostic workup is insufficient to differentiate between benign and malignant pancreatic neuroendocrine tumors (PNET). The aim of the present study was to evaluate the potential prognostic role of the promoter GTn repeat polymorphism (GTn) of the heme oxygenase-1 gene in PNET.
  
  
  METHODS
  Tumor, metastasis, corresponding healthy tissue, and peripheral blood leukocyte DNA of 46 patients who underwent surgical resection for PNET were analyzed for GTn by PCR, capillary electrophoresis, and DNA-sequencing. The GTn was correlated to clinicopathologic parameters and clinical outcome.
  
  
  RESULTS
  GTn was classified into short (<25) and long (≥ 25) alleles and three (SS, SL, and LL) genotypes were defined. There was no difference in GTn genotype among tumor, healthy tissue, metastasis, and peripheral blood leukocyte DNA. The SS and SL genotype displayed significantly more poor differentiated tumors (P = 0.001) and higher tumor recurrence rate (P = 0.0001) compared with LL patients. The LL genotype patients presented predominantly benign PNET (P < 0.001). The LL genotype had the longest disease-free (P < 0.001) and overall survival (P = 0.006). Besides the WHO classification the GTn was identified as a strong predictor of tumor recurrence (hazard ratio 3.1, 95% confidence interval 1.3-7.3) in PNET.
  
  
  CONCLUSIONS
  GTn differentiates between benign and malignant PNET and is a strong predictor of tumor recurrence.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. vashist@uke.de
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Vashist
authors.forename: Guentac
authors.initials: G
authors.lastname: Uzunoglu
authors.forename: Lena
authors.initials: L
authors.lastname: Deutsch
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Kalinin
authors.forename: Oliver
authors.initials: O
authors.lastname: Zehler
authors.forename: Adil
authors.initials: A
authors.lastname: Alzadjali
authors.forename: Asad
authors.initials: A
authors.lastname: Kutup
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Emre F
authors.initials: EF
authors.lastname: Yekebas
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016208:Databases, Factual; D005260:Female; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1