Meeting-in-the-middle using metabolic profiling - a strategy for the identification of intermediate biomarkers in cohort studies.
BACKGROUND
Predictive disease risk biomarkers that can be linked to exposure have proved difficult to identify in case-control studies.


METHODS
Parallel statistical analysis of the correlation between (1)H NMR profiles from plasma samples collected before disease onset (EPIC cohort), versus exposure to dietary compounds, and follow-up disease endpoints (colon and breast cancer) was performed.


RESULTS
Metabonomic signatures associated with colon cancer and dietary fiber intake (a protective factor according to epidemiological studies) were identified.


CONCLUSIONS
This implementation of the novel "meet-in-the-middle" analytical strategy indicates how case-control studies nested in prospectively collected cohorts may reveal intermediate biomarkers linking exposure and disease.
Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.
Marc
M
Chadeau-Hyam
Toby J
TJ
Athersuch
Hector C
HC
Keun
Maria
M
De Iorio
Timothy M D
TM
Ebbels
Mazda
M
Jenab
Carlotta
C
Sacerdote
Stephen J
SJ
Bruce
Elaine
E
Holmes
Paolo
P
Vineis
D015415:Biomarkers / Q000032:analysis / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000097:blood / Q000453:epidemiology; D004032:Diet / Q000706:statistics & numerical data; D004043:Dietary Fiber / Q000008:administration & dosage / Q000706:statistics & numerical data; D004044:Dietary Proteins / Q000008:administration & dosage; D015340:Epidemiologic Research Design; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D017720:Molecular Epidemiology; D010949:Plasma / Q000737:chemistry; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D015415:Biomarkers; D004043:Dietary Fiber; D004044:Dietary Proteins