Prognostic role of host cyclooxygenase and cytokine genotypes in a caucasian cohort of patients with gastric adenocarcinoma

García-González, M.A. ; Nicolás-Pérez, D. ; Lanas, A. (Universidad de Zaragoza) ; Bujanda, L. ; Carrera, P. ; Benito, R. (Universidad de Zaragoza) ; Strunk, M. ; Sopeña, F. (Universidad de Zaragoza) ; Santolaria, S. ; Piazuelo, E. (Universidad de Zaragoza) ; Jiménez, P. ; Campo, R. ; Espinel, J. ; Manzano, M. ; Geijo, F. ; Pellisé, M. ; González-Huix, F. ; Espinós, J. ; Zaballa, M. ; Titó, L. ; Barranco, L. ; Pazo, R. ; Quintero, E.

Resumen: 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.
Methodology: 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 polymor phisms 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.

Idioma: Inglés

DOI: 10.1371/journal.pone.0046179

Año: 2012

Publicado en: PLoS One 7, 9 (2012), e46179 [11 pp.]
ISSN: 1932-6203

Factor impacto JCR: 3.73 (2012)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 7 / 56 = 0.125 (2012) - Q1 - T1

Tipo y forma: Article (Published version)

Área (Departamento): Medicina (Departamento de Medicina, Psiquiatría y Dermatología)
Área (Departamento): Fisiología (Departamento de Farmacología y Fisiología)
Área (Departamento): Microbiología (Departamento de Microbiología, Medicina Preventiva y Salud Pública)