title: Rotating-shift nurses after a day off: peripheral clock gene expression, urinary melatonin, and serum 17-β-estradiol levels.
abstract: OBJECTIVE
  Impairment of clock gene expression and changes in melatonin and 17-β-estradiol levels may constitute biological alterations underlying the increased risk of breast cancer among shift workers. The aim of this study was to compare levels of selected core clock gene expression, 6-sulfatoxymelatonin (aMT6s), and 17-β-estradiol between rotational shift work (SW) and daytime (DT) workers after a day off.
  
  
  METHODS
  The cross-sectional study comprised 60 nurses with ≥2 years of SW and 56 permanent DT nurses. Transcript levels of circadian genes BMAL1, CLOCK, NPAS2, CRY1, CRY2, PER1, PER2, PER3, and REVERBα were determined by quantitative real-time polymerase chain reaction (PCR) in lymphocytes. All participants were tested in the early follicular phase of the menstrual cycle. Samples were collected at the beginning of the morning-shift after a regular night's sleep on a day off. Chronotype and sociodemographic characteristics were also evaluated.
  
  
  RESULTS
  We found a significantly higher expression of BMAL1, CLOCK, NPAS2, PER1, PER2, and REVERBα and a lower expression of PER3, CRY1 and CRY2 among SW compared to DT nurses. SW participants did not demonstrate a significant difference in aMT6s levels, but they did show significantly higher 17-β-estradiol levels compared to DT nurses. Multiple linear regression analysis confirmed the role of SW on expression of BMAL1 (β 0.21, P=0.040), CLOCK (β 0.35, P=0.008), NPAS2 (β 0.30, P=0.012), PER1 (β 0.33, P=0.008), PER2 (β 0.19, P=0.047), PER3 (β -0.27, P=0.012), CRY1 (β -0.33, P=0.002), CRY2 (β -0.31, P=0.005), REVERBα (β 0.19, P=0.045), and on 17-β-estradiol levels (β 0.32, P=0.003). The analysis also confirmed the role of chronotype as an independent factor for PER1 (β 0.48, P=0.001) and PER2 (β -0.22, P=0.022) expression, and 17-β-estradiol levels (β 0.26, P=0.011).
  
  
  CONCLUSIONS
  Rotating SW nurses show alterations in peripheral clock gene expression and 17-β-estradiol levels at the beginning of the morning shift after a day off.
authors.affiliation: Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/a, 60020 Torrette, Ancona, Italy. m.bracci@univpm.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bracci
authors.forename: Nicola
authors.initials: N
authors.lastname: Manzella
authors.forename: Alfredo
authors.initials: A
authors.lastname: Copertaro
authors.forename: Sara
authors.initials: S
authors.lastname: Staffolani
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Strafella
authors.forename: Mariella
authors.initials: M
authors.lastname: Barbaresi
authors.forename: Benedetta
authors.initials: B
authors.lastname: Copertaro
authors.forename: Venerando
authors.initials: V
authors.lastname: Rapisarda
authors.forename: Matteo
authors.initials: M
authors.lastname: Valentino
authors.forename: Lory
authors.initials: L
authors.lastname: Santarelli
mesh_terms: D000328:Adult; D056926:CLOCK Proteins / Q000235:genetics*; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000652:urine*; D008875:Middle Aged; D009741:Nursing Staff, Hospital; D010561:Personnel Staffing and Scheduling; D014940:Work Schedule Tolerance
chemical_list: D004958:Estradiol; D056926:CLOCK Proteins; D008550:Melatonin