Prognostic role of microRNA polymorphisms in advanced gastric cancer: a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

Ann Oncol

Department of Oncology, Haematology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen; Haematologisch-Onkologische Praxis Eppendorf, Hamburg, Germany. Electronic address:

Published: October 2013

Background: To determine the prognostic role of selected microRNA (miRNA) polymorphisms in advanced gastric cancer (AGC).

Patients And Methods: Six hundred and seventy-four AGC patients received 5-fluorouracil (F), leucovorin (L), oxaliplatin (O) or FL + cisplatin (P) or additional docetaxel (T) to FLO (FLOT) within four clinical trials. Polymorphisms of mir-26a1 (rs7372209), mir-27a (rs895819), mir-100 (rs1834306), mir-146a (rs2910164), mir-196-a2 (rs11614913), mir-219-1 (rs107822) and mir-423 (rs6505162) were genotyped. Variable selection for the final multivariate model (n = 487) was based on univariate and multivariate Cox-regression analyses with a cut-off P-value of ≤ 20%.

Results: Genetic factors significantly associated with overall survival (OS) were rs7372209 (mir-26a1) variant genotypes (hazard ratio, HR 1.307 [95% confidence interval (CI) 1.031-1.656], P = 0.0272), rs895819 (mir-27a) variant genotypes (HR 1.304 [95% CI 1.031-1.650], P = 0.0270) and rs11614913 (mir-196a2) variant genotypes (HR 0.791 [95% CI 0.625-1.000], P = 0.0497). Clinical factors with significant impact on OS were Eastern Cooperative Oncology Group (ECOG) 2 performance status (HR 1.880 [95% CI 1.254-2.820], P = 0.0023), curative surgery of advanced disease (HR 0.235 [95% CI 0.123-0.449], P < 0.0001) and addition of docetaxel in locally AGC patients (HR 0.348 [95% CI 0.145-0.838], P = 0.0301). Combined analyses revealed an improved OS in patients without any unfavourable genotype of 18 months compared with 14, 12 and 10 months in patients with 1, 2 and 3 unfavourable genotypes, respectively (P = 0.0257).

Conclusions: These data suggest a significant impact of selected miRNA polymorphisms on prognosis in AGC.

Download full-text PDF

Source
http://dx.doi.org/10.1093/annonc/mdt330DOI Listing

Publication Analysis

Top Keywords

variant genotypes
12
prognostic role
8
polymorphisms advanced
8
advanced gastric
8
gastric cancer
8
mirna polymorphisms
8
agc patients
8
patients unfavourable
8
[95%
6
role microrna
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!