IL-8-251T>A (rs4073) Polymorphism Is Associated with Prognosis in Gastric Cancer Patients.
By: Patricio Gonzalez-Hormazabal, Sandra Romero, Maher Musleh, Marco Bustamante, Juan Stambuk, Raul Pisano, Enrique Lanzarini, Hector Chiong, Jorge Rojas, Victor Gonzalo Castro, Lilian Jara, Zoltan Berger

Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Santiago, Chile patriciogonzalez@uchile.cl.
2018-08-16; doi: 10.21873/anticanres.12907
Abstract

Background/aim

Inflammation is a key process in gastric carcinogenesis. Cytokines are mediators of inflammation and are involved in metastasis and tumorigenicity. We previously assessed the role of cytokine gene polymorphisms in gastric cancer risk in Chile. In the present study, we aimed to analyze whether these polymorphisms are associated with overall survival (OS) in gastric cancer (GC) patients.

Patients

A total of 153 individuals with GC diagnosis were followed-up for at least 2 years. Hazard ratios (HR) were estimated from Cox regression models using SNPs as predictor variables. The following SNPs were genotyped for study using a TaqMan assay: rs16944 (IL1B -511C>T); rs4073 (IL8 -251 T>A); rs2275913 (IL-17 -197G>A); rs1800872 (IL10 -592 C>A); rs1800896 (IL10 -1082A>G); rs28372698 (IL32).

Results

Interleukin-8 rs4073 (IL-8 -251T>A) showed association with OS under the dominant model (TA + AA) only when adjusted by clinicopathological variables (HR=1.64, 95%CI=1.05-2.55, p=0.030, q-value=0.18), but not with the univariate model (HR=1.51, 95%CI=0.98-2.31, p=0.062, q-value=0.37). No significant differences were observed after adjusting for population stratification (PC1 and PC2 from Principal Component Analysis using genotypes from Infinium Global Screening Array). After stratification by clinicopathological variables, the association with shorter overall survival was higher among patients with diffuse-type tumors (HR=2.24, 95%CI=1.16-4.45) and patients with tumor size >5 cm (HR=1.79, 95%CI=1.08-2.97).

Conclusion

These results suggest a role of IL-8 rs4073 in cancer prognosis. Its use as a prognostic marker of GC survival warrants further investigation.



Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

PMID:30275190






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