title: Association of AMP-activated protein kinase with risk and progression of non-Hodgkin lymphoma.
abstract: BACKGROUND
  Metabolic dysregulation has been identified as an "emerging hallmark" of cancer. The heterotrimeric AMP-activated protein kinase (AMPK) complex is a central regulator of the metabolic system and an important component of the mTOR pathway and the p53 axis, making it uniquely positioned to influence carcinogenesis through its canonical functions in the metabolic arena, as well as through more traditional mechanisms such as regulation of apoptosis and angiogenesis.
  
  
  METHODS
  We conducted a population-based genetic association study to examine the impact of mutations in AMPK subunit genes on risk of non-Hodgkin lymphoma (NHL). We also analyzed public microarray data to determine the expression of AMPK in NHL cells and to assess the influence of AMPK expression on overall survival in patients with NHL.
  
  
  RESULTS
  We identified an AMPK subunit haplotype, which was significantly associated with NHL [OR, 5.44, 95% confidence interval (CI), 2.15-13.75] in women with no family history of cancer. Haplotypes in two subunits, PRKAA2 and PRKAG3, were nominally associated with the follicular and diffuse large B-cell lymphoma histologic subtypes, respectively, although these associations did not retain statistical significance after correction for multiple comparisons. Further, both of these subunits were differentially expressed (P < 0.05) in one or more lymphoma cell type, and higher expression of two versions of the AMPK-β subunit was significantly associated with increased 5-year survival among patients with NHL (P = 0.001 and P = 0.021).
  
  
  CONCLUSIONS
  These results provide evidence for AMPK involvement in the pathogenesis and progression of NHL.
  
  
  CONCLUSIONS
  These findings may lead to a novel area of research into NHL treatment and chemoprevention.
authors: Department of Epidemiology, Tulane School of Public Health and Tropical Medicine and Tulane Cancer Center, New Orleans, LA, USA.
authors: Aaron E
authors: AE
authors: Hoffman
authors: Kathryn
authors: K
authors: Demanelis
authors: Alan
authors: A
authors: Fu
authors: Tongzhang
authors: T
authors: Zheng
authors: Yong
authors: Y
authors: Zhu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008224:Lymphoma, Follicular / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C526181:PRKAA2 protein, human; C526223:PRKAG2 protein, human; C526225:PRKAG3 protein, human; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human
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