Serum folate concentration and the incidence of lung cancer

PLoS One. 2017 May 11;12(5):e0177441. doi: 10.1371/journal.pone.0177441. eCollection 2017.

Abstract

Background: Lung cancer is a leading cause of cancer-related mortality globally. Folate helps to maintain DNA integrity and to regulate gene expression. Serum folate levels may affect the risk of several cancers, including lung cancer. In this study we evaluated the association between serum folate concentration and variations in genes involved in folate metabolism with lung cancer incidence in Poland.

Methods: The study included 366 lung cancer patients and 366 control subjects. We measured serum folate concentration and genotyped six variants in MTHFR, MTR and MTRR genes. The odds ratios of being diagnosed with lung cancer were calculated using conditional univariable and multivariable logistic regression with respect to folate level and genotypes.

Results: The mean serum folate level was lower in lung cancer cases than in control group (20.07 nmol/l vs. 22.52 nmol/l, p = 0.002). The odds ratio for lung cancer declined with increasing serum content of the folate. The folate concentration of >25.71 nmol/l (IVth quartile) in comparison to <15.92 nmol/l (Ist quartile) was associated with an odds ratio of 0.61 (95%CI 0.40-0.95, p = 0.03). The analysis of variations in MTHFR, MTR and MTRR genes did not reveal any significant difference between lung cancer cases and controls in univariable and multivariable analyses.

Conclusion: In this case-control study, lower serum folate concentrations were associated with a higher risk of lung cancer diagnosis. Although previous findings have been somewhat mixed, our results add to the evidence that circulating folate levels may be an indicator of lung cancer risk.

MeSH terms

  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Ferredoxin-NADP Reductase / genetics
  • Folic Acid / blood*
  • Genotype
  • Humans
  • Incidence
  • Logistic Models
  • Lung Neoplasms / blood*
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors

Substances

  • Folic Acid
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • MTR protein, human

Grants and funding

This work was supported by National Science Centre (https://www.ncn.gov.pl/) grant DEC-2013/09/N/NZ4/02225 (KD). The funder (National Science Center; NCN) provided support in the form of research materials, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.