title: Prognostic role of host cyclooxygenase and cytokine genotypes in a Caucasian cohort of patients with gastric adenocarcinoma.
abstract: BACKGROUND
  Genetic factors influencing the prognosis of gastric adenocarcinoma (GAC) are not well known. Given the relevance of cytokines and other pro-inflammatory mediators in cancer progression and invasiveness, we aimed to assess the prognostic role of several functional cytokine and cyclooxygenase gene polymorphisms in patients with GAC.
  
  
  METHODS
  Genomic DNA from 380 Spanish Caucasian patients with primary GAC was genotyped for 23 polymorphisms in pro-inflammatory (IL1B, TNFA, LTA, IL6, IL12p40), anti-inflammatory (IL4, IL1RN, IL10, TGFB1) cytokine, and cyclooxygenase (PTGS1 and PTGS2) genes by PCR, RFLP and TaqMan assays. Clinical and histological information was collected prospectively. Survival curves were estimated by the Kaplan-Meier method and compared using the log rank test. Outcome was determined by analysis of Cox proportional hazards, adjusting for confounding factors.
  
  
  RESULTS
  The median follow-up period and median overall survival (OS) time were 9.9 months (range 0.4-120.3) and 10.9 months (95% CI: 8.9-14.1), respectively. Multivariate analysis identified tumor stages III (HR, 3.23; 95% CI:2-5.22) and IV (HR, 5.5; 95% CI: 3.51-8.63) as independent factors associated with a significantly reduced OS, whereas surgical treatment (HR: 0.44; 95%CI: 0.3-0.6) was related to a better prognosis of the disease. Concerning genetic factors, none of the 23 polymorphisms evaluated in the current study did influence survival. Moreover, no gene-environment interactions on GAC prognosis were observed.
  
  
  CONCLUSIONS
  Our results show that, in our population, the panel of selected pro- and anti-inflammatory cytokine, and cyclooxygenase gene polymorphisms are not relevant in determining the prognosis of gastric adenocarcinoma.
authors.affiliation: Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain. asgarcia@unizar.es
authors.forename: María Asunción
authors.initials: MA
authors.lastname: García-González
authors.forename: David
authors.initials: D
authors.lastname: Nicolás-Pérez
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.forename: Patricia
authors.initials: P
authors.lastname: Carrera
authors.forename: Rafael
authors.initials: R
authors.lastname: Benito
authors.forename: Mark
authors.initials: M
authors.lastname: Strunk
authors.forename: Federico
authors.initials: F
authors.lastname: Sopeña
authors.forename: Santos
authors.initials: S
authors.lastname: Santolaria
authors.forename: Elena
authors.initials: E
authors.lastname: Piazuelo
authors.forename: Pilar
authors.initials: P
authors.lastname: Jiménez
authors.forename: Rafael
authors.initials: R
authors.lastname: Campo
authors.forename: Jesús
authors.initials: J
authors.lastname: Espinel
authors.forename: Marisa
authors.initials: M
authors.lastname: Manzano
authors.forename: Fernando
authors.initials: F
authors.lastname: Geijo
authors.forename: María
authors.initials: M
authors.lastname: Pellisé
authors.forename: Ferrán
authors.initials: F
authors.lastname: González-Huix
authors.forename: Jorge
authors.initials: J
authors.lastname: Espinós
authors.forename: Manuel
authors.initials: M
authors.lastname: Zaballa
authors.forename: Llúcia
authors.initials: L
authors.lastname: Titó
authors.forename: Luis
authors.initials: L
authors.lastname: Barranco
authors.forename: Roberto
authors.initials: R
authors.lastname: Pazo
authors.forename: Enrique
authors.initials: E
authors.lastname: Quintero
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D051545:Cyclooxygenase 1 / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D015996:Survival Rate; D044465:White People
chemical_list: D016207:Cytokines; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human