III Congreso de innovación docente en clásicas en la Comunidad de Madrid: Los retos de la enseñanza online

Memoria final del PIMCD 58/202

Prognostic Role of Host Cyclooxygenase and Cytokine Genotypes in a Caucasian Cohort of Patients with Gastric Adenocarcinoma

<div><h3>Background</h3><p>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.</p> <h3>Methodology</h3><p>Genomic DNA from 380 Spanish Caucasian patients with primary GAC was genotyped for 23 polymorphisms in pro-inflammatory (<em>IL1B</em>, <em>TNFA</em>, <em>LTA</em>, <em>IL6</em>, <em>IL12p40</em>), anti-inflammatory (<em>IL4</em>, <em>IL1RN</em>, <em>IL10</em>, <em>TGFB1</em>) cytokine, and cyclooxygenase (<em>PTGS1</em> and <em>PTGS2</em>) 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.</p> <h3>Results</h3><p>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.</p> <h3>Conclusions</h3><p>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.</p> </div

Kaplan-Meier survival plots presented by (A) TNM stage, (B) surgical treatment, (C) age, (D) gender, (E) smoking habit, (F) H. pylori infection, (G) tumor location, and (H) histological subtype.

<p>Statistical analysis was performed by the log rank test.</p

Multivariate Cox proportional hazard analysis for GAC patients.

*<p>N = number of individuals. The final number of GAC patients entered in the model after excluding those individuals with missing values was 334 patients. Covariables included in the model were the following: age, gender, Charlson index, smoking habit, neoplasia site, TNM stage, surgical treatment, <i>TNFA</i> rs361525, <i>LTA</i> rs909253, <i>IL10</i> rs2243250, <i>PTGS1</i> rs5788, and <i>PTGS2</i> rs4648298 gene polymorphisms.</p

Demographic and clinicopathological characteristics of patients with GAC (n = 380).

*<p>Information was available for 344 patients.</p>**<p>Clinical tumor stages according to the International Union Against Cancer (UICC) criteria.</p><p>N = number of individuals.</p