Genetically Predicted Iron Status Correlated With Risk Of Liver Cancer

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Iron overload is a known risk factor for liver disease including liver cancer. The potential for iron overload to be a risk factor in other cancers was poorly understood.

Susanna C. Larsson of the Karolinska Institutet, Stockholm, Sweden, and colleagues carried out a two-sample Mendelian randomization study to systematically assess the possibility of causal associations of four iron status biomarkers with risk of cancer both in general and site specifically. Summary statistics from a genome-wide association study (GWAS) of iron status, the Breast Cancer Association Consortium and the UK Biobank were used. The study was published in the journal Nutrients.

Iron status predicted from genetics was associated with liver cancer and inversely associated with brain cancer. There was no association with cancer in general or any other cancer of a specific site. Iron status association with liver cancer was mainly driven by a single nucleotide polymorphism in Human homeostatic iron regulator (HFE) gene. HFE is thought to regulate circulating iron uptake by modulating the interaction of the transferrin receptor with transferrin.

Interestingly, alcoholism has been associated with iron overload with a dose response linked to liver cancer risk, however the present study did not find iron status to be driven be alcohol consumption.


Conditions and diseases associated with liver cancer such as alcoholism, and viral hepatitis, could potentially benefit from iron lowering therapies for prevention. Conversely, patients receiving long-term iron therapy for borderline anaemia to normalize iron status may be at increased risk of liver cancer. It is also a consideration for people exposed to high iron levels in water and food preparation or supplementation.

β€œThe present study showed that genetically predicted iron status was positively associated with risk of liver cancer and inversely associated with risk of brain cancer but not associated with overall cancer and a number of other site-specific cancers among European-descent individuals. These findings need to be interpreted with caution in light of the influential effect of a single variant in the HFE gene and the limited number of liver and brain cancer cases. Nevertheless, our results, along with observational data, highlight the importance of further research on the impact of adjustment of iron levels within the physiological range, through supplementation or chelation, on risk of these cancers types. In particular, careful consideration may be needed with regards to ongoing supplementation in anaemic patients or those at high risk of liver cancer,” concluded the authors.