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Author Notes:

To whom correspondence should be addressed. E-mail: krasimira.aleksandrova@dife.de.2016-03

The authors’ responsibilities were as follows—

KA, DT, and HB: designed and conducted the research

ER, HB, DT, A Trichopoulou, HBB-d-M, IR, KO, A Tjønneland, M-CB-R, DP, SP, RT, PV, PHP, EW, M-JS, M-DC, and NW: provided essential data

KA: performed the statistical analyses, wrote the manuscript, and took responsibility for the integrity of the data and accuracy of the data analysis

CB, DD, PL, A Trichopoulou, MJ, VF, IR, HBB-d-M, TP, KT, MJG, KO, A Tjønneland, M-CB-R, LD, AR, RK, TK, CT, E-MP, GS, DP, SP, SG, RT, PV, PHP, EW, ML, TB, JRQ, LL-B, M-JS, M-DC, EA, MD, LMN, M Sund, PW, BO, KEB, K-TK, NW, M Stepien, TD-S, NA, NM, ER, HB, and DT: critically revised the manuscript.

KA, CB, DD, PL, A Trichopoulou, MJ, VF, IR, HBB-d-M, TP, KT, MJG, KO, A Tjønneland, M-CB-R, LD, AR, RK, TK, CT, E-MP, GS, DP, SP, SG, RT, PV, PHP, EW, ML, TB, JRQ, LL-B, M-JS, M-DC, EA, MD, LMN, M Sund, PW, BO, KEB, K-TK, NW, M Stepien, TD-S, NA, NM, ER, HB, and DT: had full access to all study data.

We thank Ellen Kohlsdorf (EPIC-Potsdam, Germany) and Bertrand Hemon (International Agency for Research on Cancer–France) for their work on data management and technical assistance.

We thank all participants in EPIC for their outstanding cooperation.

None of the authors reported any conflicts of interest related to the study.

Subjects:

Keywords:

  • biomarkers
  • coffee
  • European Prospective Investigation into Cancer and Nutrition
  • liver cancer
  • mediation

The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition

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Journal Title:

American Journal of Clinical Nutrition

Volume:

Volume 102, Number 6

Publisher:

, Pages 1498-1508

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer—hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having ≥4 cups (600 mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and total bilirubin, which—in combination—attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.

Copyright information:

© 2015, American Society for Nutrition

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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