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J Natl Cancer Inst. 2019 Jun 5. pii: djz122. doi: 10.1093/jnci/djz122. [Epub ahead of print]

Prospective investigation of serum metabolites, coffee drinking, liver cancer incidence, and liver disease mortality.

Author information

1
Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
2
Nutrition and Metabolism Section, Biomarkers Group, International Agency for Research on Cancer (IARC), Lyon, France.
3
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Abstract

BACKGROUND:

Coffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development.

METHODS:

We measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the ATBC cohort (N = 29,133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes.

RESULTS:

Overall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% CI = 2.00-7.74) for tyrosine to 4.95 (95% CI = 2.64-9.29) for GCA and from 4.00 (95% CI = 2.42-6.62) for GCA to 6.77 (95% CI = 3.62-12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; ORs ranged from 0.16 to 0.37. Associations persisted following diet-adjustment and for outcomes occurring >10 years after blood collection.

CONCLUSIONS:

A broad range of compounds were associated with coffee drinking, incident liver cancer and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee.

KEYWORDS:

bile acids; cirrhosis; coffee; hepatocellular carcinoma; metabolomics

PMID:
31168595
DOI:
10.1093/jnci/djz122

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