Untargeted Metabolomics For The Discovery Of Plasma Biomarkers Of Coffee Intake In The EPIC Cohort

Joseph ROTHWELL, International Agency for Research on Cancer (IARC), France

1 Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
2 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA

Purpose
The consumption of coffee has been consistently associated with lower risk of cancers of the liver, endometrium and skin, as well as overall mortality. However, epidemiological studies of coffee and health typically rely on a non-specific measure of total coffee intake obtained from dietary questionnaires. It is unknown whether heterogeneity in this complex dietary component impacts these associations. The aim of this study was to use untargeted metabolomics to discover new plasma biomarkers of diverse coffee intakes in free-living subjects that may be used as an alternative or complement to questionnaire-based methods.
 
Methods
Firstly, 76 coffee brew samples were analysed by high resolution mass spectrometry coupled to liquid-chromatography (LC-MS) to identify prominent coffee compounds and evaluate differences between their profiles by species, production and preparation type. Secondly, plasma samples from 475 participants of the European Prospective Investigation into Nutrition and Cancer (EPIC) were also profiled. These subjects were from France, Germany, Italy and Greece and reported habitual coffee intake using a food frequency questionnaire. Mass spectral features whose intensities were correlated with reported coffee intake were identified using a multinomial regression, adjusting for country, sex, smoking status and alcohol consumption.
 
Results
A number of plasma metabolites correlated with high coffee consumption were identified using knowledge of coffee compounds gained by analysis of the 76 coffee brews and mining of open-source web databases. These characteristic signals included alkaloids, polyphenols, diterpenes, amino acids and aldehyde and ketone flavour compounds. Many of these are highly specific to coffee.
 
Conclusions
These biomarkers will be subsequently validated and used individually or in combination to aid coffee intake estimation in future cohort studies and to further clarify the role of coffee in cancer prevention.

Funding source
National Cancer Institute, Bethesda, USA.