title: Prognostic role of microRNA polymorphisms in advanced gastric cancer: a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
abstract: BACKGROUND
  To determine the prognostic role of selected microRNA (miRNA) polymorphisms in advanced gastric cancer (AGC).
  
  
  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.
authors: Department of Oncology, Haematology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen.
authors: L
authors: L
authors: Stenholm
authors: Department of Internal Medicine I, University Hospital Carl Gustav Carus, University of Dresden, Dresden.
authors: J
authors: J
authors: Stoehlmacher-Williams
authors: Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt.
authors: S E
authors: SE
authors: Al-Batran
authors: Department of Medical Statistics, RWTH Aachen University, Aachen.
authors: N
authors: N
authors: Heussen
authors: Department of Oncology, Haematology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen.
authors: S
authors: S
authors: Akin
authors: Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt.
authors: C
authors: C
authors: Pauligk
authors: Department of Internal Medicine I, University Hospital Carl Gustav Carus, University of Dresden, Dresden.
authors: S
authors: S
authors: Lehmann
authors: Department of Oncology, Haematology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen.
authors: T
authors: T
authors: Senff
authors: III Medical Clinic, University Hospital Mannheim, University of Heidelberg, Mannheim.
authors: R D
authors: RD
authors: Hofheinz
authors: Department of Internal Medicine I, University Hospital Carl Gustav Carus, University of Dresden, Dresden.
authors: G
authors: G
authors: Ehninger
authors: Department of Internal Medicine I, University Hospital Carl Gustav Carus, University of Dresden, Dresden.
authors: M
authors: M
authors: Kramer
authors: Department of Oncology, Haematology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen; Haematologisch-Onkologische Praxis Eppendorf, Hamburg, Germany. Electronic address: egoekkurt@hope-hamburg.de.
authors: E
authors: E
authors: Goekkurt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D013534:Survival; D043823:Taxoids / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D014803:Vitamin B Complex; D000077143:Docetaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil
keywords: advanced gastric cancer; chemotherapy; microRNA; polymorphisms; prognostic factors,