title: Genotyping of CYP3A5 polymorphisms among Bulgarian patients with sporadic colorectal cancer and controls.
abstract: BACKGROUND
  The purpose of the study was to genotype four polymorphisms in CYP3A5 (CYP3A5*2, CYP3A5*3, CYP3A5*3B, and CYP3A5*6) for a possible association between individual genetic variations and susceptibility to colorectal cancer. Another point of interest was to conduct a comprehensive analysis in tumor and normal intestine tissue from the same patient, searching for somatic hotspots.
  
  
  METHODS
  In our study, 146 Bulgarian patients with sporadic colorectal cancer and 160 healthy volunteers were enrolled. CYP3A5 polymorphisms were identified using rapid-cycle real-time amplification with allele-specific probes and subsequent melting curve analysis on a LightCycler.
  
  
  RESULTS
  The allele frequencies were comparable in both groups: frequency of CYP3A5*2 = 0.3% in patients vs. 0.6% in controls; frequency of CYP3A5*3 = 90.8% in patients vs. 93.1% in controls; in both groups no CYP3A5*3B and CYP3A5*6 variants were detected (p > 0.05). No difference was observed between genotype frequencies in tumor and surrounding normal tissues of 80 patients.
  
  
  CONCLUSIONS
  The CYP3A5 variants are unlikely to have an important functional significance in patients with colorectal cancer. The studied CYP3A5 loci do not seem to be hotspots for somatic mutation. DNA from archived tumor tissues is a valid alternative to the use of leukocyte DNA for genotyping of these polymorphisms.
authors.affiliation: Department of Medical Genetics, Medical University, Aleksandrovska University Hospital, Sofia, Bulgaria.
authors.forename: Darinka Todorova
authors.initials: DT
authors.lastname: Petrova
authors.forename: Nikolay
authors.initials: N
authors.lastname: Yaramov
authors.forename: Svetoslav
authors.initials: S
authors.lastname: Toshev
authors.forename: Petya
authors.initials: P
authors.lastname: Nedeva
authors.forename: Svilen
authors.initials: S
authors.lastname: Maslyankov
authors.forename: Nicolas
authors.initials: N
authors.lastname: von Ahsen
authors.forename: Michael
authors.initials: M
authors.lastname: Oellerich
authors.forename: Draga
authors.initials: D
authors.lastname: Toncheva
mesh_terms: D000368:Aged; D002031:Bulgaria / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
chemical_list: D003577:Cytochrome P-450 Enzyme System; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A