Iron Biomarkers, Hepcidin And Gastric Cancer Risk: The EPIC-Eurgast Study

Paula JAKSZYN, Catalan Institute of Oncology, Spain
FONSECA A. 1 , LUJAN L. 1 , ARANDA N. 2 , ARIJA V. 2 , AGUDO A. 1 , ON BEHALF OF EURGAST WORKING GROUP . 1

1 Nutrition and Cancer Unit, Catalan Institute of Oncology
2 Unitat de Nutrició i Salut Pública Facultat de Medicina i Ciències de la Salut Universitat Rovira i Virgili

Introduction: Iron, an essential element for human life but also toxic when in excess has a very well-regulated metabolism. Although evidence suggests that dietary iron is associated with gastric cancer, results from studies measuring iron biomarkers is rather insufficient to lead to any conclusions. Recently, hepcidin has been discovered as a key regulator of iron homeostasis.
Aim: To investigate the relationship between body iron biomarkers, serum hepcidin levels and gastric cancer risk.
Method / Design: We conducted a nested case-control study in the multi-centric European Prospective Investigation into Cancer and Nutrition (EPIC) 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 pre-diagnostic serum iron, ferritin, transferrin, and C-reactive protein, and hepcidin levels and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (OR) and 95% confidence intervals (CI) for the risk of gastric cancer by iron metrics were estimated from multivariate conditional logistic regression models
Results: After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2=0.80, 95% CI=0.72-0.88; and OR10%increment=0.87, 95% CI=0.78-0.97, respectively). Hepcidin levels was also inversely related to gastric cancer (OR for Q4 vs Q1 0.41, 95% CI=0.28-0.61; p for trend<0.0001).No statistical differences were found by gastric cancer localization (cardia and non-cardia) or histological (diffuse or intestinal) type. TIBC increased risk of overall gastric cancer (OR50µg/dl=1.13, 95%CI=1.02-1.2) and also with non-cardia gastric cancer and intestinal type. Additional analysis suggests that time since diagnosis of gastric cancer and pepsinogen levels could modify these findings.
Conclusions: Our results showed a decreased risk of gastric cancer related to body iron status. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.