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 journalArticle

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 ≤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
Volume22
Issue number8
DOIs
StatePublished - Aug 2013

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Sphingolipids
Case-Control Studies
Lung Neoplasms
Ceramides
Population
Confidence Intervals
Tumor Biomarkers
Tandem Mass Spectrometry
Liquid Chromatography
sphingosine 1-phosphate
Neoplasms
Cohort Studies
Smoking

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Plasma sphingolipids and lung cancer : A population-based, nested case-control study. / Alberg, Anthony J.; Armeson, Kent; Pierce, Jason S.; Bielawski, Jacek; Bielawska, Alicja; Visvanathan, Kala; Hill, Elizabeth G.; Ogretmen, Besim.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 8, 08.2013, p. 1374-1382.

Research output: Contribution to journalArticle

Alberg, AJ, Armeson, K, Pierce, JS, Bielawski, J, Bielawska, A, Visvanathan, K, Hill, EG & Ogretmen, B 2013, 'Plasma sphingolipids and lung cancer: A population-based, nested case-control study', Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 8, pp. 1374-1382. https://doi.org/10.1158/1055-9965.EPI-12-1424
Alberg, Anthony J. ; Armeson, Kent ; Pierce, Jason S. ; Bielawski, Jacek ; Bielawska, Alicja ; Visvanathan, Kala ; Hill, Elizabeth G. ; Ogretmen, Besim. / Plasma sphingolipids and lung cancer : A population-based, nested case-control study. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 8. pp. 1374-1382.
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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 ≤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.",
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AU - Alberg, Anthony J.

AU - Armeson, Kent

AU - Pierce, Jason S.

AU - Bielawski, Jacek

AU - Bielawska, Alicja

AU - Visvanathan, Kala

AU - Hill, Elizabeth G.

AU - Ogretmen, Besim

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N2 - 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.

AB - 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.

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