title: Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer.
abstract: BACKGROUND
  Lynch syndrome (LS; hereditary nonpolyposis colorectal cancer) is a common cause of hereditary colorectal cancer (CRC). CRC is the most common cancer diagnosed among males in Saudi Arabia but to the authors' knowledge there is a lack of data regarding the prevalence of LS in patients with CRC. There currently are no clear guidelines for the selection criteria for these patients to screen for LS.
  
  
  METHODS
  A comprehensive molecular characterization was performed in a cohort of 807 CRC cases by immunohistochemical and microsatellite analysis using polymerase chain reaction. BRAF mutation screening, high CpG island methylator phenotype, and analysis for germline mutations were performed in 425 CRC samples. These were all high microsatellite instability (MSI-H) samples (91 cases), all low MSI samples (143 cases), and selected cases from the microsatellite stable group (191 cases) that met revised Bethesda guidelines.
  
  
  RESULTS
  Polymerase chain reaction identified 91 MSI-H cases (11.3%) and sequencing revealed mismatch repair germline mutations in 8 CRC cases only. Of the total of 807 CRC cases, these 8 cases (0.99%) were MSI-H, met the revised Bethesda guidelines, and did not harbor BRAF mutations.
  
  
  CONCLUSIONS
  The results of the current study confirmed cases of LS in approximately 1.0% of CRC samples and reflects the efficacy of screening among MSI-H cases that lack BRAF mutations. This comprehensive study from Saudi Arabia will help in implementing a universal screening/reflex testing strategy in a clinical setting in Saudi Arabia and in conducting a national screening program that benefits both patients and their relatives.
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Abdul K
authors.initials: AK
authors.lastname: Siraj
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Sarita
authors.initials: S
authors.lastname: Prabhakaran
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Prashant
authors.initials: P
authors.lastname: Bavi
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Rong
authors.initials: R
authors.lastname: Bu
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Shaham
authors.initials: S
authors.lastname: Beg
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Mohsen Al
authors.initials: MA
authors.lastname: Hazmi
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Maha
authors.initials: M
authors.lastname: Al-Rasheed
authors.affiliation: Department of Surgery, Security Forces Hospital, Riyadh, Saudi Arabia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Assiri
authors.affiliation: Department of Surgery, Security Forces Hospital, Riyadh, Saudi Arabia.
authors.forename: Rami
authors.initials: R
authors.lastname: Sairafi
authors.affiliation: Department of Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Fouad
authors.initials: F
authors.lastname: Al-Dayel
authors.affiliation: Colorectal Unit, Department of Surgery, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Nasser
authors.initials: N
authors.lastname: Al-Sanea
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Shahab
authors.initials: S
authors.lastname: Uddin
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.|College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: Khawla S
authors.initials: KS
authors.lastname: Al-Kuraya
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics; D015897:Comorbidity; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D008877:Middle East / Q000453:epidemiology; D015995:Prevalence
keywords: Lynch syndrome (LS); colorectal cancer (CRC); hereditary nonpolyposis colorectal cancer (HNPCC); microsatellite instability (MSI); mismatch repair (MMR) genes; mutL homolog 1 (MLH1); mutS protein homolog 2 (MSH2); mutS protein homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2)