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

Jakszyn, Paula; Fonseca-Nunes, Ana; Lujan-Barroso, Leila; Aranda, Núria; Tous, Mónica; Arija, Victoria; Cross, Amanda; Bueno-De-Mesquita, Bas H.; Weiderpass, Elisabete and Kaaks, Rudolf, et al. (2017) In International Journal of Cancer 141(5). p.945-951
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... (More)

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.

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publication status
published
subject
keywords
cohort study, gastric cancer, hepcidin, iron homeostasis
in
International Journal of Cancer
volume
141
issue
5
pages
7 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:85021216286
  • wos:000404842200010
ISSN
0020-7136
DOI
10.1002/ijc.30797
language
English
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yes
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d2fefd97-8fbd-423f-9363-5ce3831703e4
date added to LUP
2017-07-31 10:40:36
date last changed
2018-01-30 15:25:40
@article{d2fefd97-8fbd-423f-9363-5ce3831703e4,
  abstract     = {<p>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.</p>},
  author       = {Jakszyn, Paula and Fonseca-Nunes, Ana and Lujan-Barroso, Leila and Aranda, Núria and Tous, Mónica and Arija, Victoria and Cross, Amanda and Bueno-De-Mesquita, Bas H. and Weiderpass, Elisabete and Kaaks, Rudolf and Sjöberg, Klas and Ohlsson, Bodil and Tumino, Rosario and Palli, Domenico and Ricceri, Fulvio and Fasanelli, Francesca and Krogh, Vittorio and Mattiello, Amalia and Jenab, Mazda and Gunter, Marc and Perez-Cornago, Aurora and Khaw, Kay Tee and Tjønneland, Anne and Olsen, Anja and Overvad, Kim and Trichopoulou, Antonia and Peppa, Eleni and Vasilopoulou, Effie and Boeing, Heiner and Sánchez-Cantalejo, Emilio and Huerta, José María and Dorronsoro,, Miren and Barricarte, Aurelio and Quirós, José Maria and Peeters, Petra H and Agudo, Antonio},
  issn         = {0020-7136},
  keyword      = {cohort study,gastric cancer,hepcidin,iron homeostasis},
  language     = {eng},
  month        = {09},
  number       = {5},
  pages        = {945--951},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Hepcidin levels and gastric cancer risk in the EPIC-EurGast study},
  url          = {http://dx.doi.org/10.1002/ijc.30797},
  volume       = {141},
  year         = {2017},
}