title: Polycyclic aromatic hydrocarbon exposure in oesophageal tissue and risk of oesophageal squamous cell carcinoma in north-eastern Iran.
abstract: OBJECTIVE
  To evaluate the association between polycyclic aromatic hydrocarbon (PAH) exposure in oesophageal epithelial tissue and oesophageal squamous cell carcinoma (ESCC) case status in an ESCC case-control study in a high-risk population in north-eastern Iran.
  
  
  METHODS
  Tissue microarrays (TMAs) of non-tumoral oesophageal biopsies from patients with biopsy-proven ESCC and gastrointestinal clinic patients with no endoscopic or biopsy evidence of ESCC (control subjects) in a rural region in north-eastern Iran were immunohistochemically stained. Immunohistochemistry was performed using monoclonal antibodies 8E11 and 5D11 raised against benzo[a]pyrene (B[a]P) diol epoxide (BPDE)-I-modified guanosine and BPDE-I-modified DNA, respectively. Staining intensity was quantified by image analysis and the average staining in three replicates was calculated. The main outcome measure was adjusted ORs with 95% CIs for the association between antibody staining intensity and ESCC case status.
  
  
  RESULTS
  Cultured ESCC cells exposed to B[a]P in vitro showed dose-dependent staining with 8E11 but not with 5D11. With 8E11, sufficient epithelial tissue was available in the TMA cores to analyse 91 cases and 103 controls. Compared with the lowest quintile of 8E11 staining in the controls, adjusted ORs for the 2nd to 5th quintiles were 2.42, 5.77, 11.3 and 26.6 (95% CI 5.21 to 135), respectively (p for trend <0.001). With 5D11, 89 cases and 101 controls were analysed. No association between staining and case status was observed (ORs for the 2nd to 5th quintiles were 1.26, 0.88, 1.06 and 1.63 (95% CI 0.63 to 4.21), p for trend=0.40).
  
  
  CONCLUSIONS
  Dramatically higher levels of 8E11 staining were observed in non-tumoral oesophageal epithelium from patients with ESCC than from control subjects. This finding strengthens the evidence for a causal role for PAHs in oesophageal carcinogenesis in north-eastern Iran.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rm 3018, Bethesda, MD 20892-7232, USA.
authors.forename: Behnoush
authors.initials: B
authors.lastname: Abedi-Ardekani
authors.forename: Farin
authors.initials: F
authors.lastname: Kamangar
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Masoud
authors.initials: M
authors.lastname: Sotoudeh
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons