Although it appears biologically plausible for
iron to be associated with gastric
carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body
iron status and
gastric cancer risk, we conducted a nested case-control study in the multicentric 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 prediagnostic serum
iron,
ferritin,
transferrin and
C-reactive protein, and further estimated total
iron-binding capacity (TIBC) and
transferrin saturation (TS). Odds ratios (
ORs) and 95% confidence intervals (CIs) for the risk of
gastric cancer by
iron metrics were estimated from multivariable conditional logistic regression models. 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; OR10%increment = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia
gastric cancer (
ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall
gastric cancer (OR50 µg/dl = 1.13, 95% CI = 1.02-1.2) and also with noncardia
gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and
gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of
gastric cancer related to higher body
iron stores as measured by serum
iron and
ferritin. Further investigation is needed to clarify the role of
iron in gastric
carcinogenesis.