Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort

Nada Assi, Marc J Gunter, Duncan C Thomas, Michael Leitzmann, Magdalena Stepien, Véronique Chajès, Thierry Philip, Paolo Vineis, Christina Bamia, Marie-Christine Boutron-Ruault, Torkjel M Sandanger, Amaia Molinuevo, Hendriek Boshuizen, Anneli Sundkvist, Tilman Kühn, Ruth Travis, Kim Overvad, Elio Riboli, Augustin Scalbert, Mazda JenabVivian Viallon, Pietro Ferrari

Research output: Contribution to journalArticle

3 Citations (Scopus)

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. This trial was registered at clinicaltrials.gov as NCT03356535.

Original languageEnglish
Pages (from-to)117-126
JournalThe American journal of clinical nutrition
Volume108
Issue number1
DOIs
Publication statusPublished - 01 Jul 2018
Externally publishedYes

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular/epidemiology
  • Case-Control Studies
  • Cohort Studies
  • Diet Surveys
  • Europe/epidemiology
  • Female
  • Healthy Lifestyle
  • Humans
  • Liver Neoplasms/epidemiology
  • Logistic Models
  • Male
  • Middle Aged
  • Risk Factors

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  • Cite this

    Assi, N., Gunter, M. J., Thomas, D. C., Leitzmann, M., Stepien, M., Chajès, V., Philip, T., Vineis, P., Bamia, C., Boutron-Ruault, M-C., Sandanger, T. M., Molinuevo, A., Boshuizen, H., Sundkvist, A., Kühn, T., Travis, R., Overvad, K., Riboli, E., Scalbert, A., ... Ferrari, P. (2018). Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort. The American journal of clinical nutrition, 108(1), 117-126. https://doi.org/10.1093/ajcn/nqy074