Dietary iron and the risk of lung cancer: A systematic review and meta-analyses of observational studies

Animal models have suggested the carcinogenic effect of iron due to its oxidative potential. The lung is particularly vulnerable to oxidative stress. However, epidemiological studies investigating the association between dietary iron and the risk of lung cancer have reported inconclusive results. In this systematic review and meta-analysis, we aimed to clarify this association. Methods: We searched PubMed, Web of Science, Scopus and Google scholar for eligible articles published through May 2023 reporting the Relative Risk (RR), Hazard Ratio (HR) or Odds Ratio (OR) with 95% confidence interval (95% CI). Case-control and cohort studies that examined the relationship between dietary iron and lung cancer risk were included and review and meta-analyses articles, experimental studies, abstracts, letters to editor and studies with insufficient data were excluded. Finally, three case-control studies and 6 cohort studies were included. Random effect models were used to calculate the pooled results. Results: Nine studies (cases n=21,943, participants n=1,542,993) were included. There were no significant associations between the highest dietary total iron (heme and non-heme) (RR: 1.09, 95% CI: 0.78 to 1.51) or heme iron (RR: 1.01, 95% CI: 0.73 to 1.38) intake compared to the lowest intake with lung cancer risk. Null-associations were also observed in the subgroup analysis based on smoking status and lung cancer histology. However, in the subgroup of women (cases n=5074), heme iron was associated with a 14% increase in the risk of lung cancer (RR: 1.14, 95% CI: 1.01 to 1.29). Conclusions: The current results demonstrated that there is no significant relationship between dietary iron intake and the risk of lung cancer. However, a positive association was observed between dietary heme iron and the risk of lung cancer in women, which may require further investigation.