Iron levels, genes involved in iron metabolism and antioxidative processes and lung cancer incidence

PLoS One. 2019 Jan 14;14(1):e0208610. doi: 10.1371/journal.pone.0208610. eCollection 2019.

Abstract

Background: Lung cancer is the most common adult malignancy accounting for the largest proportion of cancer related deaths. Iron (Fe) is an essential trace element and is a component of several major metabolic pathways playing an important role in many physiological processes. In this study we evaluated the association between Fe concentration in serum, iron metabolism parameters and genetic variaton in 7 genes involved in iron metabolism and anti-oxidative processes with the incidence of lung cancer in Poland.

Materials and methods: The study included 200 lung cancer patients and 200 matched healthy control subjects. We analyzed serum iron concentration and iron metabolism parameters (TIBC, UIBC, serum ferritin and transferrin saturation), and genotyped seven variants in seven genes: HFE, TFR1, HAMP, TF, SOD2, CAT and GPX1.

Results: Lung cancer patients compared to their matched controls had significantly higher mean serum iron level (p = 0.01), ferritin level (p = 0.007) and TIBC (p = 0.006). Analysis revealed that higher concentration of iron and ferritin (IVth quartile) compared to the lower concentration (Ist quartile) was associated with over 2-fold increased lung cancer incidence. We also found that higher transferrin saturation (p = 0.01) and lower TIBC (p<0.01) are associated with better survival of lung cancer patients. The analysis of polymorphisms in iron related genes did not reveal a significant difference between lung cancer patients and controls. However, rs10421768 in HAMP showed a borderline statistically significant correlation with lung cancer risk (OR = 2.83, p = 0.05).

Conclusions: The results of this case control study indicate that higher body iron represented by higher Fe and ferritin levels may be associated with lung cancer incidence. Rs10421768 in HAMP may be associated with about 3-times higher lung cancer risk. Higher Fe body content may be associated with better survival of lung cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism*
  • Genetic Variation
  • Humans
  • Incidence
  • Iron / blood*
  • Iron / metabolism*
  • Lung Neoplasms / blood
  • Lung Neoplasms / epidemiology*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Neoplasm Staging
  • Risk Factors
  • Survival Analysis

Substances

  • Antioxidants
  • Iron

Grants and funding

This work was supported by National Science Centre, grant no. DEC-2013/11/N/NZ4/02250. The funder Read-Gene S.A. provided support in the form of salaries for authors WM, MM and JL. The funder Strand Life Sciences provided support in the form of salaries for author SG. The funder Zdunomed provided support in the form of salaries for author PW. The specific roles of these authors are stated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.