@article{3180458,
    title = "Metabolic signature of healthy lifestyle and its relation with risk of
hepatocellular carcinoma in a large European cohort",
    author = "Assi, Nada and Gunter, Marc J. and Thomas, Duncan C. and Leitzmann, and Michael and Stepien, Magdalena and Chajes, Veronique and Philip, Thierry and and Vineis, Paolo and Bamia, Christina and Boutron-Ruault, and Marie-Christine and Sandanger, Torkjel M. and Molinuevo, Amaia and and Boshuizen, Hendriek and Sundkvist, Anneli and Kuhn, Tilman and Travis, and Ruth and Overvad, Kim and Riboli, Elio and Scalbert, Augustin and Jenab, and Mazda and Viallon, Vivian and Ferrari, Pietro",
    journal = "AMERICAN JOURNAL OF CLINICAL NUTRITION",
    year = "2018",
    volume = "108",
    number = "1",
    pages = "117-126",
    publisher = "Oxford University Press",
    issn = "0002-9165",
    doi = "10.1093/ajcn/nqy074",
    keywords = "hepatocellular carcinoma; targeted metabolomics; multivariate
statistics; metabolic signatures; partial least squares; healthy
lifestyle index; EPIC",
    abstract = "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."
}