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

Anthony J Alberg¹, Kent Armeson, Jason S Pierce

¹Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA. alberg@musc.edu

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology

|June 11, 2013

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Higher levels of sphingosine-1-phosphate (S1P) and ceramides in the blood are linked to a greater future risk of lung cancer. These findings suggest sphingolipid metabolism may play a role in lung cancer development.

Area of Science:

Biochemistry
Oncology
Metabolomics

Background:

Sphingolipids, including sphingosine-1-phosphate (S1P) and ceramides, are critical bioactive signaling molecules.
These lipids play central roles in cellular pathways implicated in cancer pathogenesis.

Purpose of the Study:

To investigate the association between prediagnostic circulating concentrations of S1P and ceramides and the risk of developing lung cancer.
To determine if sphingolipid profiles can serve as predictive biomarkers for lung cancer.

Main Methods:

A nested case-control study within the CLUE II cohort.
Assayed plasma sphingolipid levels (S1P and total ceramides) using liquid chromatography/tandem mass spectrometry (LC/MS-MS).
Matched 100 incident lung cancer cases with two cancer-free controls based on age, sex, race, and smoking status.

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Main Results:

Lung cancer cases exhibited higher plasma concentrations of S1P (2.9% increase, P=0.10) and total ceramides (5.1% increase, P=0.02) compared to controls.
Higher quartiles of S1P were associated with increased lung cancer risk (ORs ranging from 1.9 to 2.7, P=0.006).
Elevated total ceramide levels also showed a trend towards increased lung cancer risk (ORs ranging from 1.5 to 2.1, P(trend)=0.01).

Conclusions:

Elevated plasma concentrations of S1P and total ceramides are associated with an increased future risk of lung cancer.
These findings suggest that alterations in sphingolipid metabolism, including S1P generation, may be involved in the etiology of lung cancer or serve as an early indicator of the disease.