Serum iron is associated with the risk of several diseases. However, limited prospective studies have been performed between serum iron and the subsequent risk of chronic liver disease (CLD) and primary liver cancer (PLC) incidence.
We performed a nested case-control study using data from the Linxian Nutrition Intervention Trials among participants who developed PLC incidence or died from CLD over 22-years of follow-up. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of PLC incidence or CLD death in different quintile of baseline serum iron using logistic regression.
Individuals with serum iron in the highest quintile, compared to those in the second quintile (the reference), had an increased risk of CLD mortality (OR=2.02, 95% CI=1.27–3.27, P trend =0.011). The association was stronger among HCV-positive participants ( P interaction =0.005). For PLC incidence, the risk estimates were above one, but not statistically significant (all P > 0.05).
A significant positive association was found between serum iron and the risk of CLD-related mortality, especially in HCV-positive subjects. Our results suggest that serum iron plays a risk role in CLD death but not in PLC incidence.
- ● We conducted a prospective case-control study nested in NIT cohort, China.
- ● The mortality of CLD was significantly associated with serum iron.
- ● The association were stronger among HCV-positive participants.
- ● The incidence of PLC was not significantly associated with serum iron.
Liver disease has poor long-term clinical outcomes and is a major cause of illness and death worldwide . Liver cancer is the second leading cause of cancer death in China ; there are 410, 038 new cases, and 391, 152 people die from liver cancer annually . Chronic infections of hepatitis B and C virus are the predominant causes of primary liver cancer (PLC) in China .
Iron plays a pivotal role in maintaining the survival of cells . Liver is an important organ for homeostasis of iron and is also a major target organ diseases causing by iron overload, which is consistent with its essential role in iron metabolism and storage . However, excess iron is toxic to cells and tissues since excess iron could cause oxidative stress reaction, promote inflammation, and regulate cell death . In addition, high iron concentrations could improve tumor cell growth in human liver cancer cell lines .
Although, emerging evidence implicates the involvement of body iron in human chronic disease and carcinogenesis, epidemiologic studies of association between high serum iron and the risk of PLC are limited and inconclusive . It is important to evaluate the association between serum iron levels and subsequent chronic liver disease (CLD)-related mortality.
The present study was a prospective case-control study nested in the Linxian Nutrition Intervention Trial (NIT) cohorts in China. In Linxian, the esophageal/gastric cardia cancer mortality rates are among the highest in the world. The Nutrition Intervention Trial is designed to test the effectiveness of vitamin and mineral supplements in reducing the incidence of esophageal and gastric cancer . Subjects were selected from both the General Population Trial cohort and the Dysplasia Trial cohort.
In this study, we used NIT cohort population to examine the associations between prediagnostic serum iron levels and the risks of PLC incidence and CLD mortality. In addition, we examined whether hepatitis virus infection had potential joint effects on these associations.