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

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
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DOI:
10.1002/mc.21962
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发表时间:
2013-11-01
影响因子:
4.6
通讯作者:
Kim, Nam Keun
Kim, Nam Keun
中科院分区:
医学2区
文献类型:
--
作者:
Ahn, Dae Ho;Rah, HyungChul;Kim, Nam Keun

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我们研究了四种常见的microRNA多态性(miR-146 aC>G [rs 2910164]、miR-149 T>C [rs 2292832]、miR-196 a2 T>C [rs 11614913]和miR-499 A>G [rs3746444])是否与韩国人群胃癌的易感性和预后相关。在一项病例对照研究(461例患者; 447例对照)中,通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析确定了韩国人群中的四种microRNA单核苷酸多态性(SNP)。当患者被分层为弥漫型和胃肠道型胃癌组时,具有miR-499 AG和AG+GG基因型的受试者具有弥漫型胃癌的降低的校正比值比(AOR)(AOR=0.54,95%置信区间[CI]=0.31-0.97; AOR=0.57,95% CI=0.33-0.97)。在胃癌风险分层分析中,miR-146 aGG和CG+GG基因型与非吸烟者胃癌风险增加相关,而miR-149 TC和TC+CC基因型显示男性胃癌风险较低。miR-196 a2 CC基因型与女性胃癌风险升高相关。在胃癌预后方面,miR-146 aCG +GG基因型胃癌患者的生存率显著高于CC基因型患者(log-rank P=0.030),miR-499 AA基因型患者的生存率显著高于AG+GG基因型患者(log-rank P=0.013)。当miR-146 aCG +GG和miR-499 AA基因型组合时,韩国人群中的胃癌患者的存活率(对数秩PG)和预后(miR-146 aC>G和miR-499 A>G)根据胃癌类型而升高。(c)2012 Wiley Periodicals,Inc.
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 PG) and prognosis (miR-146aC>G and miR-499A>G) in the Korean population depending on gastric cancer type. (c) 2012 Wiley Periodicals, Inc.