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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 1H 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. Conclusion: 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.