Plasma sphingolipids and lung cancer: A population-based, nested case-control study

Anthony J. Alberg, Kent Armeson, Jason S. Pierce, Jacek Bielawski, Alicja Bielawska, Kala Visvanathan, Elizabeth G. Hill, Besim Ogretmen

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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 ≤70C 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 (Ptrend = 0.01). Conclusions: Higher concentrations of S1P and total ceramide in plasma were associated with increased future risk of lung cancer. Impact: 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. Cancer Epidemiol Biomarkers Prev; 22(8); 1374-82.

Original languageEnglish (US)
Pages (from-to)1374-1382
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Issue number8
StatePublished - Aug 2013

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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