title: Toenail iron, genetic determinants of iron status, and the risk of glioma.
abstract: OBJECTIVE
  Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case-control study.
  
  
  METHODS
  Samples were collected a median of 24 days following glioma diagnosis in the cases (10th-90th percentile, range: 10-44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes.
  
  
  RESULTS
  No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ~3 weeks of diagnosis (OR = 0.93; 95 % CI 0.46, 1.87 comparing those with high (≥14 μg/g) vs. low (<6 μg/g) iron levels). In contrast, an inverse association with increasing iron was observed after restricting to cases with a delay of 3 weeks or greater (OR = 0.42; 95 % CI 0.19, 0.95), reflecting potentially insidious effects of advancing disease on iron levels among the cases. No associations were observed for any of the examined genetic variants.
  
  
  CONCLUSIONS
  The results do not support a role for body iron stores as a determinant of glioma risk.
authors.affiliation: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA, gabriella.anic@nih.gov.
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Anic
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Madden
authors.forename: Reid C
authors.initials: RC
authors.lastname: Thompson
authors.forename: L Burton
authors.initials: LB
authors.lastname: Nabors
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olson
authors.forename: Renato V
authors.initials: RV
authors.lastname: Larocca
authors.forename: James E
authors.initials: JE
authors.lastname: Browning
authors.forename: John D
authors.initials: JD
authors.lastname: Brockman
authors.forename: Peter A
authors.initials: PA
authors.lastname: Forsyth
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Egan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005293:Ferritins / Q000097:blood; D005500:Follow-Up Studies; D005838:Genotype; D005910:Glioma / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019266:Iron, Dietary; D008297:Male; D008875:Middle Aged; D009262:Nails / Q000737:chemistry*; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D019266:Iron, Dietary; D009363:Neoplasm Proteins; D005293:Ferritins; D007501:Iron