Metabolic Signature of Healthy Lifestyle and HCC
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Observational

Summary: 
      Hepatocellular carcinoma (HCC) is the most common form of liver cancer and its incidence is
      increasing including in regions where hepatitis infection rates are low. This trend may be
      the result of increases in 'unhealthy lifestyle' factors. The main aim of this study is to
      identify metabolic signatures associated with healthy lifestyle behaviours and to relate
      these signatures to risk of developing HCC to investigate whether the metabolites were of
      predictive utility for HCC beyond data procured from questionnaires. To address this
      question, we exploited data from a large European cohort (EPIC) which includes detailed
      questionnaire-based data as well as metabolomic data.
    

Detailed description: 
      Studies using metabolomic data have identified metabolites from several compound classes that
      are associated with disease-related lifestyle factors. This study identified metabolic
      signatures reflecting lifestyle patterns and related them to hepatocellular carcinoma (HCC)
      risk in the EPIC cohort. Partial Least Squares (PLS) analysis related seven modified Healthy
      Lifestyle Index variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes,
      hepatitis) to 132 targeted serum-measured metabolites, and a liver function score in a nested
      study of HCC with 147 case-control pairs. The association between the resulting PLS scores
      and HCC risk was examined in multivariable conditional logistic regression models where odds
      ratios (OR) and their 95% confidence intervals (95%CI) were computed. The PLS-derived
      lifestyle component reflected a high propensity towards healthy behaviours. Its metabolic
      counterpart was positively related to the following metabolites: SM(OH) C14:1, C16:1 and
      C22:2, and negatively to glutamate, hexoses, and PC aaC32:1. The lifestyle and metabolomics
      components were inversely associated with HCC risk with OR for a 1-SD increase in scores
      equal to 0.49(95%CI=0.35 to 0.68) and 0.28(0.18 to 0.43).

      Measuring a specific metabolites panel may identify strata of the population at higher risk
      for HCC and can add substantial discrimination compared to questionnaire data
    

Observational model: Case-Control
Time perspective: Prospective
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 administrative centres in 10 European countries including Denmark, France, Germany,
        Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom.

        This analysis focused on a nested case-control study of 147 cases of HCC and 147 matched
        controls with available biological samples.
      
Biospecimen description: 
      Serum samples
    
Keywords: targeted metabolomics; multivariate statistics; metabolic signatures; partial least squares; healthy lifestyle index; EPIC