title: Gastric cancers of Western European and African patients show different patterns of genomic instability.
abstract: BACKGROUND
  Infection with H. pylori is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of H. pylori infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA), in an attempt to support the African enigma hypothesis at the biological level.
  
  
  METHODS
  DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis.
  
  
  RESULTS
  Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p < 0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p = 0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK and Caucasian SA patients and between native and Caucasian SA patients.
  
  
  CONCLUSIONS
  Gastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.
authors.affiliation: Dept. of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Tineke E
authors.initials: TE
authors.lastname: Buffart
authors.forename: Melanie
authors.initials: M
authors.lastname: Louw
authors.forename: Nicole C T
authors.initials: NC
authors.lastname: van Grieken
authors.forename: Marianne
authors.initials: M
authors.lastname: Tijssen
authors.forename: Beatriz
authors.initials: B
authors.lastname: Carvalho
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.forename: Heike
authors.initials: H
authors.lastname: Grabsch
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Schalk W
authors.initials: SW
authors.lastname: van der Merwe
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
mesh_terms: D000328:Adult; D000349:Africa; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics*; D043171:Chromosomal Instability; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D042822:Genomic Instability; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D013019:South Africa; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D006113:United Kingdom