title: Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries.
abstract: OBJECTIVE
  The epidemiology of colorectal carcinoma is well known to differ among countries but the molecular characteristics are usually assumed to be similar. International differences in molecular pathology have not been studied extensively but have implications for the management of patients in different countries and of immigrant patients.
  
  
  METHODS
  We evaluated the CpG island methylator phenotype pathway characterized by concordant methylation of gene promoters that often silences transcription of the genes, the microsatellite instability pathway, and K-ras and p53 gene status in 247 colorectal carcinomas from the three selected Middle Eastern countries of Egypt, Jordan, and Turkey.
  
  
  RESULTS
  Colorectal carcinoma from Egypt had the lowest frequencies of methylation. In multinomial logistic regression analysis, Jordanian colorectal carcinoma more frequently had methylation involving the p16 tumor suppressor gene (odds ratio, 3.5; 95% confidence interval, 1.2-10.6; P = 0.023) and MINT31 locus (odds ratio, 2.3; 95% confidence interval, 1.0-5.1; P = 0.041). The K-ras proto-oncogene was more frequently mutated in colorectal carcinoma from Turkey (odds ratio, 2.9; 95% confidence interval, 1.2-6.7; P = 0.016), but p53 overexpression was more common in both Jordanian and Turkish colorectal carcinoma than in Egyptian cases (odds ratio, 2.5; 95% confidence interval, 1.2-5.5; P = 0.019; and odds ratio, 3.6; 95% confidence interval, 1.8-7.1; P = 0.0003, respectively). The findings in Turkish colorectal carcinoma were most similar to those reported for Western cases.
  
  
  CONCLUSIONS
  Colorectal carcinoma from Middle Eastern countries have differing gene methylation patterns and mutation frequencies that indicate dissimilar molecular pathogenesis, probably reflecting different environmental exposures. These molecular differences could affect prevention strategies, therapeutic efficacy, and transferability of clinical trial results.
authors.affiliation: Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Annie O
authors.initials: AO
authors.lastname: Chan
authors.forename: Amr S
authors.initials: AS
authors.lastname: Soliman
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bedeir
authors.forename: P Scott
authors.initials: PS
authors.lastname: Houlihan
authors.forename: Nadia
authors.initials: N
authors.lastname: Mokhtar
authors.forename: Nidal
authors.initials: N
authors.lastname: Al-Masri
authors.forename: Ugur
authors.initials: U
authors.lastname: Ozbek
authors.forename: Rami
authors.initials: R
authors.lastname: Yaghan
authors.forename: Ayten
authors.initials: A
authors.lastname: Kandilci
authors.forename: Sherif
authors.initials: S
authors.lastname: Omar
authors.forename: Yersu
authors.initials: Y
authors.lastname: Kapran
authors.forename: Ferhunde
authors.initials: F
authors.lastname: Dizdaroglu
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Bondy
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Issa
authors.forename: Bernard
authors.initials: B
authors.lastname: Levin
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Hamilton
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002288:Adenocarcinoma, Mucinous / Q000453:epidemiology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018276:Carcinoma, Medullary / Q000453:epidemiology / Q000235:genetics; D018279:Carcinoma, Signet Ring Cell / Q000453:epidemiology / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D004534:Egypt / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D019942:Genes, p16 / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007597:Jordan / Q000453:epidemiology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction; D014421:Turkey / Q000453:epidemiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D000070957:MutL Protein Homolog 1