Genetic variations in PRKAA1 predict the risk and progression of gastric Cancer

BMC Cancer. 2018 Sep 25;18(1):923. doi: 10.1186/s12885-018-4818-3.


Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Gastric cancer; PRKAA1; Polymorphism; Prognosis.

MeSH terms

  • AMP-Activated Protein Kinases / genetics*
  • Aged
  • Alleles
  • Case-Control Studies
  • Disease Progression
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality


  • AMP-Activated Protein Kinases
  • PRKAA1 protein, human