ABSTRACT
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.
