title: Association between common genetic variants in pre-microRNAs and prognosis of advanced gastric cancer treated with chemotherapy.
abstract: BACKGROUND
  Common single-nucleotide polymorphisms (SNPs) in pre-miRNAs (hsa-mir-196a2, hsa-mir-146a and hsa-mir-499) have been associated with various malignancies and their prognoses. We evaluated the associations of three selected SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (hsa-mir-196a2, hsa-mir-146a and hsa-mir-499) with the prognosis of advanced gastric cancers (GCs) treated by chemotherapy.
  
  
  METHODS
  The rs11614913 (T>C), rs2910164 (C>T), and rs3746444 (A>G) SNPs were genotyped in 130 advanced GCs performing chemotherapy. Survival and response evaluation was based on overall survival (OS) and progression-free survival (PFS). Response rate (RR) was also evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST).
  
  
  RESULTS
  63 patients performed gastrectomy after chemotherapy (neoadjuvant chemotherapy) and the remaining cases performed chemotherapy alone as treatment (chemotherapy alone). The majority of cases performed S-1-based chemotherapy as the first line treatment (n=119, 92%). The rs3746444 (A>G) SNP was significantly associated with OS by the log-rank test (p=0.018), while other SNPs were not associated with OS. The rs3746444 (A>G) SNP was also associated with OS and PFS among cases of neoadjuvant chemotherapy (p=0.038, 0.024, respectively). Multivariate survival analysis using the Cox's regression model revealed that non-responder by the RECIST (Hazard ratio (HR): 2.14 95%CI 1.06-4.19), upper third cancer (HR: 2.48 95%CI 1.12-5.49) and more advanced stage (HR: 4.12 95%CI 1.06-16.02) were predictive factors for worse OS, while the rs3746444 A allele carrier was predictive factor for better OS (HR: 0.33 95%CI 0.18-0.75).
  
  
  CONCLUSIONS
  The rs3746444 A allele carrier in the hsa-mir-499 is associated with better prognosis in advanced GC performing chemotherapy.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan tomomiccyu@yahoo.co.jp.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sumi
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Ishizuka
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohmiya
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012322:RNA Precursors / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D035683:MicroRNAs; D012322:RNA Precursors
keywords: Gastric cancer; Hsa-mir-499; chemotherapy; microRNA; polymorphism; rs3746444