Clinical trial NCT03402568: Alcohol Consumption and Circulating Metabolites
Official title: Circulating Metabolites Associated With Alcohol Intake in the European Prospective Investigation Into Cancer and Nutrition Cohort
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: No Condition, Focus: Metabolites of Alcohol Consumption
Keywords: alcohol
targeted metabolomics
lipid metabolites
amino acids
acylcarnitines
Lead sponsor: International Agency for Research on Cancer
Sponsor class: OTHER
Collaborators: name: Maastricht University
name: Imperial College London
name: Danish Cancer Society
name: University of Aarhus
name: Centre for Research in Epidemiology and Population Health (CESP)
name: Gustave Roussy, Cancer Campus, Grand Paris
name: German Cancer Research Center
name: German Institute of Human Nutrition
name: Hellenic Health Foundation
name: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: ISPO Cancer Prevention and Research Institute
name: Federico II University
name: HuGeF Foundation
name: Azienda Sanitaria Provinciale Ragusa
name: University of Tromso
name: Institut Català d'Oncologia
name: Ministry of Health - Government of the Principality of Asturias
name: Andalusian School of Public Health
name: Universidad de Murcia
name: Instituto de Salud Pública Gobierno de Navarra
name: Subdirección de Salud Pública de Gipuzkoa
name: Skane University Hospital
name: Umeå University
name: MORGEN-EPIC, Bilthoven
name: Prospect-EPIC, Utrecht
name: University of Oxford
name: University of Cambridge
First posted: 2018-01-18
Enrollment: 2974
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Over 520,000 healthy men and women aged 25-85 were enrolled between 1992 and 2000 across 23 EPIC centres in 10 European countries including Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom.

This study used data from 2,974 control participants from four case-control studies on colorectal (n=491), hepatobiliary (n=327), kidney (n=635), and prostate cancer (n=1,521) nested in the EPIC cohort, for which targeted metabolomics data had been acquired.

Brief summary: Alcohol consumption is a risk factor for numerous health conditions and an important cause of death. Identifying metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. The objective of this study is to investigate associations of alcohol consumption with circulating concentrations of 123 metabolites including amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins. For this purpose, the investigators use data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and applied a discovery and replication approach.

Detailed description: This study used data from 2,974 control participants from four case-control studies on colorectal (n=491), hepatobiliary (n=327), kidney (n=635), and prostate cancer (n=1,521) nested in the EPIC cohort, for which targeted metabolomics data had been acquired. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry using the BIOCRATES AbsoluteIDQTM p180 kit. Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of ln-transformed alcohol consumption with Z-standardized ln-transformed residual metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value\<0.05) were further tested in the replication set (Bonferroni-corrected p-value\<0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 metabolites were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Associations with acylcarnitines and phosphatidylcholines were generally positive, while mostly inverse associations were observed with citrulline and sphingomyelins.

This study adds novel knowledge regarding circulating metabolites associated with alcohol consumption, and provides leads for further studies into the underlying biological mechanisms. A better understanding of metabolic pathways affected by alcohol consumption may contribute to the development of mechanism-tailored intervention strategies to prevent and treat alcohol-related conditions. Furthermore, it may help to identify biomarkers of alcohol consumption facilitating early preventive strategies in individuals at-risk for developing alcohol-related morbidities.

Eligibility criteria: Inclusion Criteria (for EPIC):

* Aged 30-70
* Healthy volunteers residing within defined geographical areas (where study centers are located). Different settings by centre; mostly general population with some exceptions: women of a health insurance company for teachers and school workers (France), women attending breast cancer screening (Utrecht-The Netherlands, and Florence-Italy), mainly blood donors (most centers in Italy and Spain) and a cohort consisting predominantly of vegetarians (the 'health-conscious' group in Oxford, UK).

Exclusion criteria (for this study):

* Individuals without metabolomics data
* Individuals without data on alcohol consumption at recruitment

Primary outcomes:
measure: Circulating metabolite concentrations
timeFrame: Laboratory analyses performed between Oct 2012-Oct 2016
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
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