TY - JOUR
TI - Metabolic signature of healthy lifestyle and its relation with risk of
hepatocellular carcinoma in a large European cohort
AU - Assi, Nada
AU - Gunter, Marc J.
AU - Thomas, Duncan C.
AU - Leitzmann,
AU - Michael
AU - Stepien, Magdalena
AU - Chajes, Veronique
AU - Philip, Thierry
AU - and Vineis, Paolo
AU - Bamia, Christina
AU - Boutron-Ruault,
AU - Marie-Christine
AU - Sandanger, Torkjel M.
AU - Molinuevo, Amaia and
AU - Boshuizen, Hendriek
AU - Sundkvist, Anneli
AU - Kuhn, Tilman
AU - Travis,
AU - Ruth
AU - Overvad, Kim
AU - Riboli, Elio
AU - Scalbert, Augustin
AU - Jenab,
AU - Mazda
AU - Viallon, Vivian
AU - Ferrari, Pietro
JO - AMERICAN JOURNAL OF CLINICAL NUTRITION
PY - 2018
VL - 108
TODO - 1
SP - 117-126
PB - Oxford University Press
SN - 0002-9165
TODO - 10.1093/ajcn/nqy074
TODO - hepatocellular carcinoma; targeted metabolomics; multivariate
statistics; metabolic signatures; partial least squares; healthy
lifestyle index; EPIC
TODO - Background: Studies using metabolomic data have identified metabolites
from several compound classes that are associated with disease-related
lifestyle factors.
Objective: In this study, we identified metabolic signatures reflecting
lifestyle patterns and related them to the risk of hepatocellular
carcinoma (HCC) in the European Prospective Investigation into Cancer
and Nutrition (EPIC) cohort.
Design: Within a nested case-control study of 147 incident HCC cases and
147 matched controls, partial least squares (PLS) analysis related 7
modified healthy lifestyle index (HLI) variables (diet, BMI, physical
activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132
targeted serum-measured metabolites and a liver function score. The
association between the resulting PLS scores and HCC risk was examined
in multivariable conditional logistic regression models, where ORs and
95% CIs were computed.
Results: The lifestyle component’s PLS score was negatively associated
with lifetime alcohol, BMI, smoking, and diabetes, and positively
associated with physical activity. Its metabolic counterpart was
positively related to the metabolites sphingomyelin (SM)(OH) C14: 1,
C16: 1, and C22: 2 and negatively related to glutamate, hexoses, and the
diacyl-phosphatidylcholine PC aaC32: 1. The lifestyle and metabolomics
components were inversely associated with HCC risk, with the ORs for a
1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28
(0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and
0.74 (0.69, 0.80), respectively.
Conclusions: This study identified a metabolic signature reflecting a
healthy lifestyle pattern which was inversely associated with HCC risk.
The metabolic profile displayed a stronger association with HCC than did
the modified HLI derived from questionnaire data. Measuring a specific
panel of metabolites may identify strata of the population at higher
risk for HCC and can add substantial discrimination compared with
questionnaire data.
ER -