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.

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.

• Authors: Tomomitsu Tahara, Masaaki Okubo, Tomoyuki Shibata, Tomohiko Kawamura, Kazuya Sumi, Takamitsu Ishizuka, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomiyasu Arisawa, Naoki Ohmiya, Ichiro Hirata
• Journal: Anticancer research (Anticancer Res) Vol. 34 Issue 9 Pg. 5199-204 (Sep 2014) ISSN: 1791-7530 [Electronic] Greece
• PMID: 25202115 (Publication Type: Journal Article)
• Copyright: Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• MicroRNAs
• RNA Precursors

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Female
• Genetic Variation
• Humans
• Male
• MicroRNAs (genetics)
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Polymorphism, Single Nucleotide
• Prognosis
• RNA Precursors (genetics)
• Stomach Neoplasms (drug therapy, genetics, mortality, pathology)
• Treatment Outcome