Hepcidin levels and gastric cancer risk in the EPIC-EurGast study

Paula Jakszyn, Ana Fonseca-Nunes, Leila Lujan-Barroso, Núria Aranda, Mónica Tous, Victoria Arija, Amanda Cross, H. Bas Bueno-de-Mesquita, Elisabete Weiderpass, Tilman Kühn, Rudolf Kaaks, Klas Sjöberg, Bodil Ohlsson, Rosario Tumino, Domenico Palli, Fulvio Ricceri, Francesca Fasanelli, Vittorio Krogh, Amalia Mattiello, Mazda JenabMarc Gunter, Aurora Perez-Cornago, Kay Tee Khaw, Anne Tjønneland, Anja Olsen, Kim Overvad, Antonia Trichopoulou, Eleni Peppa, Effie Vasilopoulou, Heiner Boeing, Emilio Sánchez-Cantalejo, José María Huerta, Miren Dorronsoro, Aurelio Barricarte, José Maria Quirós, Petra H. Peeters, Antonio Agudo

Research output: Contribution to journalArticlepeer-review

Abstract

Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93–0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: −69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.

Original languageEnglish
Pages (from-to)945-951
Number of pages7
JournalInternational Journal of Cancer
Volume141
Issue number5
DOIs
Publication statusPublished - Sep 1 2017

Keywords

  • cohort study
  • gastric cancer
  • hepcidin
  • iron homeostasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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