A Metabolome-Wide Association Study Of Alcohol Consumption And Smoking In The Epic Cohort

Eline VAN ROEKEL, Maastricht University, Netherlands
ASSI N. 2 , CARAYOL M. 2 , ACHAINTRE D. 2 , RINALDI S. 2 , STEPIEN M. 2 , WEIJENBERG M. 1 , SCALBERT A. 2 , JENAB M. 2 , FERRARI P. 2

1 Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
2 Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France

Purpose: Alcohol consumption and smoking are among the main modifiable risk factors for cancer and many other chronic conditions worldwide. The exact biological mechanisms through which these lifestyle behaviors affect human health and metabolism need further investigation. Metabolomic approaches allow an agnostic exploration of novel associations of risk factors with human metabolites and metabolic pathways. Our aim was to study associations of alcohol consumption and smoking habits with concentrations of a set of 130 targeted blood metabolites.
 
Methods: The study population consisted of 327 control subjects from a nested case-control study on hepatocellular carcinoma within the European Prospective Investigation into Cancer (EPIC). Alcohol consumption and smoking habits were based on self-report assessments. The Biocrates AbsoluteIDQTM p180 kit and tandem mass spectrometry were used to measure serum concentrations of 11 acylcarnitines, 20 amino acids, hexose, 79 phosphatidylcholines, 14 sphingomyelins, and 5 biogenic amines. Multivariable linear regression analyses were performed to study confounder-adjusted associations of categories of alcohol consumption and smoking habits with metabolite concentrations, using false discovery rate correction for multiple testing.
 
Results: Study subjects (56% men) had a mean age of 59.6 years (5th-95th percentile: 47.5-72.7). In multivariable models, moderate-to-heavy alcohol consumption (>15 and >30 grams/day in women and men, respectively) compared to light alcohol consumption (0.1-15 grams/day and 0.1-30 grams/day, respectively) was statistically significantly associated (q-value<0.05) with higher concentrations of 2 lyso-phosphatidylcholines and 3 diacyl-phosphatidylcholines and lower concentrations of 3 acyl-alkyl-phospatidylcholines and 4 sphingomyelins. None of the metabolites were significantly associated with current or former smoking compared to never smoking.      
 
Conclusions: Our results indicate that alcohol consumption may affect sphingo- and phospholipid metabolism. Replication of our findings together with research aiming at elucidating biological mechanisms will be key to relate sets of identified metabolites with the development of cancer and other chronic conditions. 
 
Funding source: Dutch Cancer Society.