title: Association of the miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G polymorphisms with gastric cancer risk and survival in the Korean population.
abstract: We investigated whether four common microRNA polymorphisms (miR-146aC>G [rs2910164], miR-149T>C [rs2292832], miR-196a2T>C [rs11614913], and miR-499A>G [rs3746444]) are associated with the susceptibility and prognosis of gastric cancer in the Korean population. The four microRNA single-nucleotide polymorphisms (SNPs) were identified in a case-control study (461 patients; 447 controls) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in the Korean population. When patients were stratified into diffuse and intestinal-type gastric cancer groups, subjects with the miR-499AG and AG + GG genotypes had reduced adjusted odds ratios (AORs) for diffuse-type gastric cancer (AOR = 0.54 with 95% confidence interval [CI] = 0.31-0.97; AOR = 0.57 with 95% CI = 0.33-0.97). In the stratified analyses for gastric cancer risk, the miR-146aGG and CG + GG genotypes were associated with increased risk of gastric cancers among the non-smokers, whereas the miR-149TC and TC + CC genotypes showed lower risk of gastric cancer in males. The miR-196a2CC genotype was associated with elevated gastric cancer risk among females. For gastric cancer prognosis, intestinal-type gastric cancer patients with miR-146aCG + GG genotypes had significantly higher survival rates (log-rank P = 0.030) than patients with the CC genotype, and patients with the miR-499AA genotype had significantly increased survival rates compared to patients with the AG + GG genotypes (log-rank P = 0.013). When miR-146aCG + GG and miR-499AA genotypes were combined, the survival rate of intestinal-type gastric cancer patients was elevated (log-rank P < 0.001). No association was found between gastric or diffuse-type cancer prognosis and other miRNAs. Our data demonstrate that specific miRNA SNPs are associated with gastric cancer susceptibility (miR-499A>G) and prognosis (miR-146aC>G and miR-499A>G) in the Korean population depending on gastric cancer type.
authors.affiliation: Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Ahn
authors.forename: HyungChul
authors.initials: H
authors.lastname: Rah
authors.forename: Young-Kook
authors.initials: YK
authors.lastname: Choi
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Min
authors.forename: KyuBum
authors.initials: K
authors.lastname: Kwack
authors.forename: Sung Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Hwang
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C542542:MIRN146 microRNA, human; C551557:MIRN149 microRNA, human; C542543:MIRN196 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs