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Gut 2010;59:1178-1183 doi:10.1136/gut.2010.210609
  • Oesophagus

Polycyclic aromatic hydrocarbon exposure in oesophageal tissue and risk of oesophageal squamous cell carcinoma in north-eastern Iran

  1. Behnoush Abedi-Ardekani1,2,3,4,
  2. Farin Kamangar1,2,5,
  3. Stephen M Hewitt6,
  4. Pierre Hainaut3,
  5. Masoud Sotoudeh1,
  6. Christian C Abnet2,
  7. Philip R Taylor2,
  8. Paolo Boffetta7,8,
  9. Reza Malekzadeh1,
  10. Sanford M Dawsey2
  1. 1Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
  2. 2Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  3. 3Molecular Carcinogenesis Cluster, International Agency for Research on Cancer, Lyon, France
  4. 4Social Security Organization, Tehran, Islamic Republic of Iran
  5. 5Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland, USA
  6. 6Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA
  7. 7Genetics and Epidemiology Cluster, International Agency for Research on Cancer, Lyon, France
  8. 8Tisch Cancer Institute, Mount Sinai School of Medicine, New York, USA
  1. Correspondence to Sanford M Dawsey, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rm 3018, Bethesda, Maryland, 20892-7232, USA; dawseys{at}mail.nih.gov

  1. Contributors All authors contributed to the conception and design of the study. BA-A, FK, SMH, PH, MS, CCA and SMD participated in data collection and assembly. BA-A, FK and CCA analysed the data. All authors contributed to data interpretation and the writing of the manuscript.

  • Revised 22 April 2010
  • Accepted 29 April 2010
  • Published Online First 28 June 2010

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.

Footnotes

  • Funding This work was supported by intramural funds from the Digestive Disease Research Center of Tehran University of Medical Sciences, the National Cancer Institute at the National Institutes of Health and the International Agency for Research on Cancer.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the National Cancer Institute at the National Institutes of Health, the International Agency for Research on Cancer and the Digestive Disease Research Center of Tehran University of Medical Sciences and all participants gave written informed consent before enrolment in the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Revised 22 April 2010
  • Accepted 29 April 2010
  • Published Online First 28 June 2010

This Article

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  4. All Versions of this Article:
    1. gut.2010.210609v1
    2. 59/9/1178 most recent

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