Serum Biomarkers of Iron Status and Risk of Primary Liver Cancer: A Systematic Review and Meta-Analysis

Kim Tu Tran*, Helen G. Coleman, Robert Stephen McCain, Chris R. Cardwell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
391 Downloads (Pure)


Hereditary hemochromatosis, a disease which causes iron overload, has been shown to increase liver cancer risk but the association between serum iron levels within non-hemochromatosis population and liver cancer risk is unclear. We investigated this association by conducting a systematic review and meta-analysis. Medline, Embase, and Scopus were searched to identify articles published up to January 2019. The search incorporated terms for liver cancer (hepatocellular and cholangiocarcinoma) and for serum iron (iron, ferritin, and transferrin). Briefly, nested case-control or cohort studies were included if they recorded a measure of iron, prior to diagnosis, and contained liver cancer patients and controls. Meta-analysis techniques were used to calculate pooled hazard ratios (HRs) and investigate heterogeneity between studies. Nine relevant studies were identified. There was evidence of an association between high serum ferritin and primary liver cancer risk (six studies, HR 1.49, 95% CI 1.13, 1.96) and high serum iron and primary liver cancer risk (three studies, HR 2.47 95% CI 1.31, 4.63). However, these associations were subject to heterogeneity (I 2 = 62%, P = 0.02 and I 2 =80%, P = 0.007, respectively). In conclusion, we found some evidence that increased iron levels was associated with primary liver cancer. The cause of this association merits additional research.

Original languageEnglish
JournalNutrition and Cancer
Early online date02 May 2019
Publication statusEarly online date - 02 May 2019

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research


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