title: Epigenetics could explain some Moroccan population colorectal cancers peculiarities: microsatellite instability pathway exploration.
abstract: BACKGROUND
  Colorectal Cancers (CRC) are one of the most common malignancies in the world. Their incidence in Morocco, between 2005 and 2007, was 5.6 for 100000 inhabitants, which is very low compared to what found in developed countries. In addition, CRCs show a high frequency of rectal localizations, and occurs in a younger population in Morocco compared to what found in developed countries. The purpose of this study is to confirm these CRC peculiarities in Morocco and try to explain them by exploring the microsatellite instability molecular pathway.
  
  
  METHODS
  This is a prospective observational study conducted since January 2010, including 385 patients admitted in Hassan II University Hospital of Fez. We collected clinical, radiological and pathological data. We investigated the expression of mismatch repair (MMR) proteins in 214 patients and BRAF gene mutations in 159 patients.
  
  
  RESULTS
  Mean age was 55.08 +/- 15.16 years. 36.5% of patients were less than 50 years old and 49.3% of tumors were localized in the rectum. Loss of MMR protein expression was observed in 11.2% of cases. It was independently associated with individual or family history of cancer belonging to Hereditary Non-Polyposis Colorectal Cancer (HNPCC) spectrum (p = 0.01) and proximal localization (p = 0.02). No BRAF mutation was detected in all cases.
  
  
  CONCLUSIONS
  These results confirm the high occurrence of CRCs to young patients and the high frequency of rectal localizations in Moroccan population. They mostly show an absence of BRAF mutation, supposing a rarity of MLH1 promoter hypermethylation pathway, which may even partially explain the CRC peculiarities in our context.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5868184711716884.
authors.affiliation: Department of pathology, University hospital Hassan II of Fez, Fez, Morocco. doc.med@hotmail.com.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sekal
authors.affiliation: Department of pathology, University hospital Hassan II of Fez, Fez, Morocco. ameurtesse@yahoo.com.
authors.forename: Hassania
authors.initials: H
authors.lastname: Ameurtesse
authors.affiliation: Department of pathology, University hospital Hassan II of Fez, Fez, Morocco. chbanil@yahoo.fr.
authors.forename: Laila
authors.initials: L
authors.lastname: Chbani
authors.affiliation: Department of molecular genetics, University hospital Hassan II of Fez, Fez, Morocco. ouldim@yahoo.fr.
authors.forename: Karim
authors.initials: K
authors.lastname: Ouldim
authors.affiliation: Department of molecular genetics, University hospital Hassan II of Fez, Fez, Morocco. sabennis@yahoo.fr.
authors.forename: Sanae
authors.initials: S
authors.lastname: Bennis
authors.affiliation: Department of gastroenterology, University hospital Hassan II of Fez, Fez, Morocco. yassine.abkari@gmail.com.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Abkari
authors.affiliation: Department of molecular genetics, University hospital Hassan II of Fez, Fez, Morocco. gasparo_v@hotmail.fr.
authors.forename: Amal
authors.initials: A
authors.lastname: Boulouz
authors.affiliation: Department of gastroenterology, University hospital Hassan II of Fez, Fez, Morocco. dafrb@yahoo.fr.
authors.forename: Dafr Allah
authors.initials: DA
authors.lastname: Benajah
authors.affiliation: Department of visceral surgery, University hospital Hassan II of Fez, Fez, Morocco. benjelloun19@hotmail.com.
authors.forename: Basher
authors.initials: B
authors.lastname: Benjelloun
authors.affiliation: Department of visceral surgery, University hospital Hassan II of Fez, Fez, Morocco. ousadden@yahoo.fr.
authors.forename: Abdelmalek
authors.initials: A
authors.lastname: Ousadden
authors.affiliation: Department of visceral surgery, University hospital Hassan II of Fez, Fez, Morocco. khaittaleb@gmail.com.
authors.forename: Khalid
authors.initials: K
authors.lastname: Ait Taleb
authors.affiliation: Department of visceral surgery, University hospital Hassan II of Fez, Fez, Morocco. aitlaalims@yahoo.fr.
authors.forename: Said
authors.initials: S
authors.lastname: Ait Laalim
authors.affiliation: Department of visceral surgery, University hospital Hassan II of Fez, Fez, Morocco. toughiman@hotmail.com.
authors.forename: Imane
authors.initials: I
authors.lastname: Toghrai
authors.affiliation: Department of visceral surgery, University hospital Hassan II of Fez, Fez, Morocco. khali.mazaz@gmail.com.
authors.forename: Khalid
authors.initials: K
authors.lastname: Mazaz
authors.affiliation: Department of oncology, University hospital Hassan II of Fez, Fez, Morocco. drsarifi@yahoo.fr.
authors.forename: Samia
authors.initials: S
authors.lastname: Arifi
authors.affiliation: Department of oncology, University hospital Hassan II of Fez, Fez, Morocco. mellasnawfel@yahoo.fr.
authors.forename: Nawfel
authors.initials: N
authors.lastname: Mellas
authors.affiliation: Department of epidemiology, University hospital Hassan II of Fez, Fez, Morocco. elrhazikarima@gmail.com.
authors.forename: Karima
authors.initials: K
authors.lastname: El Rhazi
authors.affiliation: Department of pathology, University hospital Hassan II of Fez, Fez, Morocco. taoufhar@yahoo.fr.
authors.forename: Taoufiq
authors.initials: T
authors.lastname: Harmouch
authors.affiliation: Department of gastroenterology, University hospital Hassan II of Fez, Fez, Morocco. gastrochufes@hotmail.com.
authors.forename: Sidi Adil
authors.initials: SA
authors.lastname: Ibrahimi
authors.affiliation: Department of pathology, University hospital Hassan II of Fez, Fez, Morocco. amartiafaf@gmail.com.
authors.forename: Afaf
authors.initials: A
authors.lastname: Amarti Riffi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics; D000230:Adenocarcinoma / Q000737:chemistry / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000453:epidemiology / Q000235:genetics*; D019175:DNA Methylation; D053843:DNA Mismatch Repair / Q000235:genetics*; D004252:DNA Mutational Analysis; D003906:Developing Countries; D005260:Female; D020022:Genetic Predisposition to Disease; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009018:Morocco / Q000453:epidemiology; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1