Genetic variations in PRKAA1 predict the risk and progression of gastric Cancer.
Genetic variations in PRKAA1 predict the risk and progression of gastric Cancer.
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PRKAA1 的遗传变异可预测胃癌的风险和进展。
DOI：
10.1186/s12885-018-4818-3
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发表时间：
2018-09-25
期刊：
影响因子：
3.8
通讯作者：
Lu P
中科院分区：
文献类型：
--
作者：
Chen M;Jiang B;He B;Tang M;Wang P;Chen L;Lu J;Lu P
PRKAA1编码5- amp活化蛋白激酶(AMPK) α-亚基，该亚基与胃癌的发病机制有关。以往的研究表明，PRKAA1基因多态性可能与非心源性胃癌（NCGC）的发生风险相关，但PRKAA1基因多态性是否与胃癌的临床病理特征及其临床结局相关，在很大程度上尚不清楚。我们进行了一项病例对照研究，包括481名胃癌患者和490名健康对照者。利用Sequenom MassARRAY平台对所登记多态性进行基因型鉴定。本研究显示rs10074991 GG基因型（校正后OR = 1.44, 95%CI: 0.99-2.09, p = 0.056）与加性模型结果（校正后OR = 1.21, 95%CI: 1.01-1.46, p = 0.042）具有显著的边缘增高的胃癌风险。同样，rs13361707 TC基因型也会增加胃癌的风险（校正OR = 1.47, 95%CI: 1.01-2.14, p = 0.043；加性模型校正OR = 1.22, 95%CI: 1.02-1.47, p = 0.033）。此外，rs154268和rs461404也被发现与胃癌风险增加相关，这可能受年龄、肿瘤类型和分化以及肿瘤分期的影响。单倍型分析显示，A-G-C-T-C-G单倍型（rs6882903、rs10074991、rs13361707、rs3805490、rs154268和rs461404）与胃癌风险增加相关（OR = 1.29, 95%CI: 1.02 ~ 1.62, p = 0.035）。总生存期（OS）的单因素分析显示，rs10074991和rs13361707变异与NCGC患者的不良OS相关。本病例对照研究提供了rs13361707cc、rs10074991GG、rs461404GG和rs154268CC与胃癌风险增加相关的证据，特别是对于NCGC，携带rs10074991G或rs13361707C等位基因的患者OS较差。本文的在线版本（10.1186/s12885-018-4818-3）包含补充资料，仅供授权用户使用。
PRKAA1 encodes α-subunit of 5-AMP-activated protein kinase (AMPK), which has been implicated in the pathogenesis of carcinoma of the stomach. Previous works have suggested that polymorphisms in the PRKAA1 may be associated with the risk of non-cardiac gastric cancer (NCGC), but whether PRKAA1 polymorphisms are related to clinical pathologic characteristics of gastric cancer and its clinical outcome is largely unknown. We carried out a case-control study including a total of 481 gastric cancer patients and 490 healthy controls. The genotypes of enrolled polymorphisms were identified with Sequenom MassARRAY platform. This study showed that rs10074991 GG genotype (adjusted OR = 1.44, 95%CI:0.99–2.09, p = 0.056) has a borderline significantly increased risk for gastric cancer, which was consistent with the result of additive model (adjusted OR = 1.21, 95%CI:1.01–1.46, p = 0.042). In similar, an increased risk of gastric cancer was also observed for rs13361707 TC genotype (adjusted OR = 1.47, 95%CI: 1.01–2.14, p = 0.043; additive model: adjusted OR = 1.22, 95%CI: 1.02–1.47, p = 0.033). Furthermore, the rs154268 and rs461404 were also found associated with increased gastric cancer risk, which may be influenced by age, tumor type and differentiation, and tumor stage. Haplotype analysis indicated A-G-C-T-C-G haplotype (rs6882903, rs10074991, rs13361707, rs3805490, rs154268 and rs461404) is associated with increased risk of gastric cancer (OR = 1.29, 95%CI: 1.02–1.62, p = 0.035). The univariate analysis for overall survival (OS) revealed that both of rs10074991 and rs13361707 variants are associated with poor OS in patients with NCGC. This case-control study provided the evidence thatrs13361707CC, rs10074991GG, rs461404GG, and rs154268CC are associated with increased gastric cancer risk, especially for NCGC, and that patients with rs10074991 G or rs13361707 C allele have a poor OS. The online version of this article (10.1186/s12885-018-4818-3) contains supplementary material, which is available to authorized users.
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