Association between common genetic variants in pre-MicroRNAs and prognosis of advanced gastric cancer treated with chemotherapy

Tomomitsu Tahara, Masaaki Okubo, Tomoyuki Shibata, Tomohiko Kawamura, Kazuya Sumi, Takamitsu Ishizuka, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomiyasu Arisawa, Naoki Ohmiya, Ichiro Hirata

Research output: Contribution to journalArticle

14 Citations (Scopus)

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. Materials and 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). Conclusion: The rs3746444 A allele carrier in the hsa-mir-499 is associated with better prognosis in advanced GC performing chemotherapy.

Original languageEnglish
Pages (from-to)5199-5204
Number of pages6
JournalAnticancer research
Volume34
Issue number9
Publication statusPublished - 01-09-2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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