Department of Radiotherapy & Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu Province, China.
Department of Critical Care Medicine, The affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, Jiangsu Province, China.
BMC Cancer. 2018 Sep 25;18(1):923. doi: 10.1186/s12885-018-4818-3.
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.
PRKAA1 编码 5-AMP 激活蛋白激酶（AMPK）的 α 亚基，该激酶已被牵连到胃癌的发病机制中。先前的研究表明，PRKAA1 中的多态性可能与非贲门胃癌（NCGC）的风险相关，但 PRKAA1 多态性是否与胃癌的临床病理特征及其临床结局相关仍知之甚少。
我们进行了一项病例对照研究，共纳入了 481 例胃癌患者和 490 例健康对照者。采用Sequenom MassARRAY 平台鉴定纳入的多态性的基因型。
本研究表明 rs10074991 GG 基因型（调整后的 OR=1.44，95%CI：0.99-2.09，p=0.056）对胃癌有显著的边缘风险增加，这与加性模型的结果一致（调整后的 OR=1.21，95%CI：1.01-1.46，p=0.042）。同样，rs13361707 TC 基因型也观察到胃癌风险增加（调整后的 OR=1.47，95%CI：1.01-2.14，p=0.043；加性模型：调整后的 OR=1.22，95%CI：1.02-1.47，p=0.033）。此外，rs154268 和 rs461404 也与胃癌风险增加相关，这可能受年龄、肿瘤类型和分化程度以及肿瘤分期的影响。单体型分析表明 A-G-C-T-C-G 单体型（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）。单因素分析总生存期（OS）显示，rs10074991 和 rs13361707 变异均与 NCGC 患者的不良 OS 相关。
本病例对照研究提供了证据表明 rs13361707CC、rs10074991GG、rs461404GG 和 rs154268CC 与胃癌风险增加相关，特别是与 NCGC 相关，并且 rs10074991 G 或 rs13361707 C 等位基因的患者 OS 较差。
