title: Allele Frequencies of the Epidermal Growth Factor Receptors Polymorphism R521K in Colorectal Cancer Patients and Healthy Subjects Indicate a Risk-Reducing Effect of K521 in Syrian Population.
abstract: BACKGROUND
  Colorectal cancer contributes heavily to cancer morbidity and mortality worldwide. Numerous therapies are currently in use, including monoclonal antibodies against cellular components involved in tumorigenesis such as epidermal growth factor receptors (EGFRs). Studies showed the polymorphism [R521K] GàA in the EGFR gene to be involved in both colorectal cancer susceptibility and clinical response to therapeutics (e.g., Cetuximab).
  
  
  OBJECTIVE
  We aimed at uncovering allele frequencies of this polymorphism among Syrian colorectal cancer patients and healthy individuals.
  
  
  METHODS
  Forty-seven patients with colorectal cancer were included in a case-control study along with 48 healthy subjects, all native Syrians. Individuals were genotyped using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were statistically analyzed to elucidate significant differences between the two groups.
  
  
  RESULTS
  Allele frequencies were 40.4% (G/G), 57.4% (G/A) and 2.1% (A/A) in colorectal cancer patients and 41.6% (G/G), 43.7% (G/A) and 14.5% (A/A) in healthy subjects. The A/A genotype was significantly lower in colorectal cancer patients than in the control group.
  
  
  CONCLUSIONS
  Homozygosity for the A allele is linked to reducing the risk of developing colorectal cancer in Syrian patients. The lower prevalence of (A/A) locally may predict sub-optimal rates of clinical response to Cetuximab compared with populations with higher frequencies of the A allele. Larger scale investigations are needed for a stronger conclusion.
authors.affiliation: Department of Pharmacology, University of Aleppo, Aleppo, Syria.
authors.forename: Ola Haj
authors.initials: OH
authors.lastname: Mustafa
authors.forename: Abdul Rezzak
authors.initials: AR
authors.lastname: Hamzeh
authors.forename: Lina
authors.initials: L
authors.lastname: Ghabreau
authors.forename: Nizar
authors.initials: N
authors.lastname: Akil
authors.forename: Ala-Eddin
authors.initials: AE
authors.lastname: Almoustafa
authors.forename: Amal
authors.initials: A
authors.lastname: Alachkar
keywords: Colorectal cancer; Epidermal growth factor receptor; Polymorphism; R521K; Syrian