title: Carcinogenic nitrosamines in traditional beer as the cause of oesophageal squamous cell carcinoma in black South Africans.
abstract: BACKGROUND
  Before the 1930s, squamous cell carcinoma (SCC) of the oesophagus was almost unknown among black South Africans. From the 1930s the annual frequency rose. A dietary cause was sought, the staple diet of black people having changed from sorghum to maize (corn), with traditional beer being brewed from maize. Carcinogenic N-nitrosamines in traditional beer were suggested as a cause of SCC of the oesophagus, with Fusarium moniliforme, a corn saprophyte, thought to play a role.
  
  
  OBJECTIVE
  To confirm the presence of N-nitrosamines in traditional beer and demonstrate a mechanism for the oncogenesis of oesophageal carcinoma.
  
  
  METHODS
  Analysis by high-performance liquid chromatography was conducted for the identification of nitrosamines in traditional beer samples, and molecular docking studies were employed to predict the affinity between N-nitrosamines and the S100A2 protein.
  
  
  RESULTS
  Carcinogenic N-nitrosamines were identified in all six samples of traditional beer examined (N=18 analyses), and docking studies confirmed a high affinity of the nitrosamine N-nitrosopyrrolidone with the S100A2 protein. This may result in the altered expression of the S100A2 protein, leading to tumour progression and prognosis.
  
  
  CONCLUSIONS
  It is suggested that carcinogenic N-nitrosamines in traditional beer are a major factor in the causation of SCC of the oesophagus in black South Africans. N-nitrosamines have been shown to produce cancer experimentally, but there has not been conclusive epidemiological evidence that N-nitrosamines are carcinogenic to humans. This study is the first to demonstrate the potential link between N-nitrosamines and a human tumour.
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa. viness.pillay@wits.ac.za.
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Charles
authors.initials: C
authors.lastname: Isaacson
authors.forename: Pride
authors.initials: P
authors.lastname: Mothobi
authors.forename: Martin
authors.initials: M
authors.lastname: Hale
authors.forename: Lomas Kumar
authors.initials: LK
authors.lastname: Tomar
authors.forename: Charu
authors.initials: C
authors.lastname: Tyagi
authors.forename: Mario
authors.initials: M
authors.lastname: Altini
authors.forename: Yahya Essop
authors.initials: YE
authors.lastname: Choonara
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
mesh_terms: D001515:Beer / Q000032:analysis*; D044383:Black People; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000208:ethnology; D002630:Chemotactic Factors / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004938:Esophageal Neoplasms / Q000139:chemically induced* / Q000208:ethnology; D006801:Humans; D062105:Molecular Docking Simulation; D009242:N-Nitrosopyrrolidine / Q000494:pharmacology; D009602:Nitrosamines / Q000009:adverse effects* / Q000032:analysis / Q000494:pharmacology; D009418:S100 Proteins / Q000378:metabolism; D013019:South Africa
chemical_list: D002273:Carcinogens; D002630:Chemotactic Factors; D009602:Nitrosamines; D009418:S100 Proteins; C098997:S100A2 protein, human; D009242:N-Nitrosopyrrolidine