TY - JOUR
T1 - Hepcidin levels and gastric cancer risk in the EPIC-EurGast study
AU - Jakszyn, Paula
AU - Fonseca-Nunes, Ana
AU - Lujan-Barroso, Leila
AU - Aranda, Núria
AU - Tous, Mónica
AU - Arija, Victoria
AU - Cross, Amanda
AU - Bueno-De-Mesquita, Bas H.
AU - Weiderpass, Elisabete
AU - Kaaks, Rudolf
AU - Sjöberg, Klas
AU - Ohlsson, Bodil
AU - Tumino, Rosario
AU - Palli, Domenico
AU - Ricceri, Fulvio
AU - Fasanelli, Francesca
AU - Krogh, Vittorio
AU - Mattiello, Amalia
AU - Jenab, Mazda
AU - Gunter, Marc
AU - Perez-Cornago, Aurora
AU - Khaw, Kay Tee
AU - Tjønneland, Anne
AU - Olsen, Anja
AU - Overvad, Kim
AU - Trichopoulou, Antonia
AU - Peppa, Eleni
AU - Vasilopoulou, Effie
AU - Boeing, Heiner
AU - Sánchez-Cantalejo, Emilio
AU - Huerta, José María
AU - Dorronsoro,, Miren
AU - Barricarte, Aurelio
AU - Quirós, José Maria
AU - Peeters, Petra H
AU - Agudo, Antonio
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - cohort study
KW - gastric cancer
KW - hepcidin
KW - iron homeostasis
UR - http://www.scopus.com/inward/record.url?scp=85021216286&partnerID=8YFLogxK
U2 - 10.1002/ijc.30797
DO - 10.1002/ijc.30797
M3 - Article
C2 - 28543377
AN - SCOPUS:85021216286
SN - 0020-7136
VL - 141
SP - 945
EP - 951
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 5
ER -
