Prognostic role of microRNA polymorphisms in advanced gastric cancer patients.

Abstract

10552 Background: As little is known about the impact of microRNA (mir) polymorphisms on prognosis of advanced gastric cancer (AGC) we sought to determine their impact on overall survival (OS) in these patients (pts). Methods: Pts were treated with either 5-fluorouracil, leucovorin and oxaliplatin (FLO) or with additional docetaxel (FLOT) in frame of a phase III or 3 phase II trials of the Arbeitsgemeinschaft Internistische Onkologie. All pts consented genetic analyses. DNA was extracted from whole blood samples (n=515) and polymorphisms of mir26a1 (rs7372209), mir27a (rs895819), mir100 (rs1834306), mir125a (rs12975333), mir146a (rs2910164), mir196a2 (rs11614913), mir219-1 (rs107822) and mir423 (rs6505162) were genotyped using PCR-based methods. Hetero- and homozygous variant genotypes were grouped versus homozygous wild type genotypes. Selection of clinical and genetic parameters for the final multivariate model was based on univariate and multivariate Cox-regression analyses with a cut-off value of p < 0.25 and included 498 pts. Results: Median age was 67 (range 23 to 86) years. 42% were treated with FLO and 58% with FLOT with a median OS of 14 months. Multivariate analyses revealed following associations: Genetic factors significantly associated with OS were mir26a1 variant genotypes (HR 1.3 [95%CI (1.01;1.6), p=.025]), mir27a variant genotypes (HR 1.3 [95%CI (1.01;1.6), p=.036]) and mir196a2 variant genotypes (HR 0.8 [95%CI (0.6;0.99), p=.046]). Clinical factors with significant impact on OS were ECOG 2 performance status (HR 1.9 [95%CI (1.3;2.8), p=.002]), curative surgery of advanced disease (HR 0.3 [95%CI (0.1;0.5), p<.001]) and locally advanced disease (HR 0.5 [95%CI (0.3;0.7), p<.001]). Combined analyses of the identified adverse genotypes of mir26a1, mir27a and mir196a2 resulted in a median OS of 9, 13, 14 and 17 months for pts with 0 (n=72), 1 (n=193), 2 (n=171) and 3 (n=54) adverse genotypes (p=.029), respectively. Conclusions: In addition to established clinical factors, mir26a1, mir27a and mir196a2 polymorphisms were significantly associated with OS. Our data suggest a strong impact of these mir polymorphisms on prognosis in AGC and might be of help for a better guidance of treatment decisions.