title: Plasma sphingolipids and lung cancer: a population-based, nested case-control study.
abstract: BACKGROUND
  Sphingosine-1-phosphate (S1P) and ceramides are bioactive signaling sphingolipids that regulate pathways that are central to cancer pathogenesis.
  
  
  METHODS
  A nested case-control study was implemented to test whether prediagnostic circulating concentrations of S1P and ceramides were associated with future lung cancer risk. In the community-based CLUE II cohort study in Washington County, Maryland, the study consisted of 100 incident lung cancer cases, each matched to two cancer-free controls on age, sex, race, and cigarette smoking status. Plasma stored at -70°C at the beginning of follow-up in 1989 was assayed for sphingolipids using liquid chromatography/tandem mass spectrometry methodology (LC/MS-MS).
  
  
  RESULTS
  Compared with controls, geometric mean plasma concentrations of S1P and total ceramides were 2.9% (P = 0.10) and 5.1% (P = 0.02), respectively, greater in lung cancer cases. For S1P, the ORs and 95% confidence intervals (CI) for lung cancer risk were 2.7 (1.2-5.9), 2.7 (1.1-6.4), and 1.9 (0.8-4.5) for the second, third, and highest fourth, respectively, compared with the lowest fourth (overall P = 0.006). Compared with those with total ceramide concentrations in the lowest fourth, the ORs (and 95% CI) for lung cancer risk were 1.6 (0.7-3.3), 1.5 (0.7-3.4), and 2.1 (0.9-4.7) for the second, third, and highest fourth, respectively (P(trend) = 0.01).
  
  
  CONCLUSIONS
  Higher concentrations of S1P and total ceramide in plasma were associated with increased future risk of lung cancer.
  
  
  CONCLUSIONS
  These novel findings suggest that perturbation of sphingolipid metabolism and S1P generation may either contribute to the etiology of lung cancer or be a marker of latent lung cancer.
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA. alberg@musc.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Alberg
authors.forename: Kent
authors.initials: K
authors.lastname: Armeson
authors.forename: Jason S
authors.initials: JS
authors.lastname: Pierce
authors.forename: Jacek
authors.initials: J
authors.lastname: Bielawski
authors.forename: Alicja
authors.initials: A
authors.lastname: Bielawska
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Hill
authors.forename: Besim
authors.initials: B
authors.lastname: Ogretmen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D002518:Ceramides / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000453:epidemiology; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D013107:Sphingolipids / Q000097:blood*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D002518:Ceramides; D008246:Lysophospholipids; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine