Alcohol Consumption and Circulating Metabolites

Circulating Metabolites Associated With Alcohol Intake in the European Prospective Investigation Into Cancer and Nutrition Cohort

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.

Study Overview

• Status: Completed
• Conditions: No Condition, Focus: Metabolites of Alcohol Consumption

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.

• Study Type: Observational
• Enrollment (Actual): 2974

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating metabolite concentrations	Blood concentrations of 123 metabolites including amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins (BIOCRATES AbsoluteIDQTM p180 kit).	Laboratory analyses performed between Oct 2012-Oct 2016

Collaborators and Investigators

• Sponsor: International Agency for Research on Cancer
• Collaborators: Universidad de Murcia; Federico II University; University of Tromso; Imperial College London; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; University of Aarhus; University of Oxford; Umeå University; German Cancer Research Center; Danish Cancer Society; University of Cambridge; Maastricht University; Skane University Hospital; Gustave Roussy, Cancer Campus, Grand Paris; Andalusian School of Public Health; German Institute of Human Nutrition; Centre for Research in Epidemiology and Population Health (CESP); Hellenic Health Foundation; Azienda Sanitaria Provinciale Ragusa; ISPO Cancer Prevention and Research Institute; HuGeF Foundation; Catalan Institute of Oncology, Barcelona; Ministry of Health - Government of the Principality of Asturias; Instituto de Salud Pública Gobierno de Navarra; Subdirección de Salud Pública de Gipuzkoa; MORGEN-EPIC, Bilthoven; Prospect-EPIC, Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2012
• Primary Completion (Actual): October 26, 2016
• Study Completion (Actual): October 26, 2016

Study Registration Dates

• First Submitted: January 10, 2018
• First Submitted That Met QC Criteria: January 10, 2018
• First Posted (Actual): January 18, 2018

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: January 19, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: alcohol; amino acids; targeted metabolomics; lipid metabolites; acylcarnitines
• Additional Relevant MeSH Terms: Drinking Behavior; Alcohol Drinking
• Other Study ID Numbers: PP201712-35

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No