Clinical trial NCT03356535: Metabolic Signature of Healthy Lifestyle and HCC
Official title: Metabolic Signature of Healthy Lifestyle and Its Relationship With Risk of Hepatocellular Carcinoma in a Large European Cohort
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatocellular Carcinoma
Keywords: targeted metabolomics
multivariate statistics
metabolic signatures
partial least squares
healthy lifestyle index
EPIC
Lead sponsor: International Agency for Research on Cancer
Sponsor class: OTHER
Collaborators: name: Imperial College London
name: Danish Cancer Society
name: University of Aarhus
name: Centre for Research in Epidemiology and Population Health (CESP)
name: Gustave Roussy, Cancer Campus, Grand Paris
name: German Cancer Research Center
name: German Institute of Human Nutrition
name: Hellenic Health Foundation
name: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: ISPO Cancer Prevention and Research Institute
name: Federico II University
name: HuGeF Foundation
name: Azienda Sanitaria Provinciale Ragusa
name: University of Tromso
name: Institut Català d'Oncologia
name: Ministry of Health - Government of the Principality of Asturias
name: Andalusian School of Public Health
name: Universidad de Murcia
name: Instituto de Salud Pública Gobierno de Navarra
name: Subdirección de Salud Pública de Gipuzkoa
name: Skane University Hospital
name: Umeå University
name: MORGEN-EPIC, Bilthoven
name: Prospect-EPIC, Utrecht
name: University of Oxford
name: University of Cambridge
First posted: 2017-11-29
Enrollment: 294
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
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.

Brief 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

Eligibility criteria: Inclusion Criteria:

* Aged 30-70
* Healthy volunteers residing within defined geographical areas (where study centers are located). Different settings by centre; mostly general population with some exceptions: women of a health insurance company for teachers and school workers (France), women attending breast cancer screening (Utrecht-The Netherlands, and Florence-Italy), mainly blood donors (most centers in Italy and Spain) and a cohort consisting predominantly of vegetarians (the 'health-conscious' group in Oxford, UK)

Primary outcomes:
measure: Hepatocellular Carcinoma
timeFrame: Follow-up started at date of entry to the study and finished at date of diagnosis, death or last completed follow-up (from December 2004 up to June 2010). Cancer incidence was determined through population cancer registries or through active follow-up.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Assi N, Gunter MJ, Thomas DC, Leitzmann M, Stepien M, Chajes V, Philip T, Vineis P, Bamia C, Boutron-Ruault MC, Sandanger TM, Molinuevo A, Boshuizen H, Sundkvist A, Kuhn T, Travis R, Overvad K, Riboli E, Scalbert A, Jenab M, Viallon V, Ferrari P. Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort. Am J Clin Nutr. 2018 Jul 1;108(1):117-126. doi: 10.1093/ajcn/nqy074.