miR-146aC>G、miR-149T>C、miR-196a2T>C 和 miR-499A>G 多态性与韩国人群胃癌风险和生存的关联。
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.
机构信息
Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
出版信息
Mol Carcinog. 2013 Nov;52 Suppl 1:E39-51. doi: 10.1002/mc.21962. Epub 2012 Sep 21.
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.
我们研究了四个常见的 microRNA 多态性(miR-146aC>G [rs2910164]、miR-149T>C [rs2292832]、miR-196a2T>C [rs11614913] 和 miR-499A>G [rs3746444])是否与韩国人群胃癌的易感性和预后相关。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析,在韩国人群中对 461 例患者(病例组)和 447 例对照(对照组)进行了这四个 microRNA 单核苷酸多态性(SNP)的鉴定。当将患者分为弥漫型和肠型胃癌组时,miR-499AG 和 AG+GG 基因型的受试者弥漫型胃癌的校正比值比(AOR)降低(AOR=0.54,95%置信区间[CI]为 0.31-0.97;AOR=0.57,95%CI=0.33-0.97)。在胃癌风险的分层分析中,miR-146aGG 和 CG+GG 基因型与非吸烟者胃癌风险增加相关,而 miR-149TC 和 TC+CC 基因型则与男性胃癌风险降低相关。miR-196a2CC 基因型与女性胃癌风险升高相关。对于胃癌预后,miR-146aCG+GG 基因型的肠型胃癌患者的生存率显著高于 CC 基因型患者(对数秩检验 P=0.030),而 miR-499AA 基因型患者的生存率显著高于 AG+GG 基因型患者(对数秩检验 P=0.013)。当 miR-146aCG+GG 和 miR-499AA 基因型结合时,肠型胃癌患者的生存率升高(对数秩检验 P<0.001)。其他 microRNA 与胃癌或弥漫型胃癌的预后无关。我们的数据表明,特定的 microRNA SNP 与韩国人群的胃癌易感性(miR-499A>G)和预后(miR-146aC>G 和 miR-499A>G)相关,具体取决于胃癌的类型。