title: Genetic variability in CYP3A4 and CYP3A5 in primary liver, gastric and colorectal cancer patients.
abstract: BACKGROUND
  Drug-metabolizing enzymes play a role in chemical carcinogenesis through enzymatic activation of procarcinogens to biologically reactive metabolites. The role of gene polymorphisms of several cytochrome P450 enzymes in digestive cancer risk has been extensively investigated. However, the drug-metabolizing enzymes with the broader substrate specificity, CYP3A4 and CYP3A5, have not been analyzed so far. This study aims to examine associations between common CYP3A4 and CYP3A5 polymorphisms and digestive cancer risk.
  
  
  METHODS
  CYP3A4 and CYP3A5 genotypes were determined in 574 individuals including 178 patients with primary liver cancer, 82 patients with gastric cancer, 151 patients with colorectal cancer, and 163 healthy individuals.
  
  
  RESULTS
  The variant allele frequencies for patients with liver cancer, gastric cancer, colorectal cancer and healthy controls, respectively, were: CYP3A4*1B, 4.8 % (95% C.I. 2.6-7.0), 3.7 % (0.8-6.6) 4.3% (2.0-6.6) and 4.3% (2.1-6.5); CYP3A5*3, 91.8 % (93.0-97.4), 95.7% (92.6-98.8), 91.7% (88.6-94.8) and 90.8% (87.7-93.9). The association between CYP3A4*1B and CYP3A5*3 variant alleles did not significantly differ among patients and controls. No differences in genotypes, allele frequencies, or association between variant alleles were observed with regard to gender, age at diagnosis, tumour site or stage.
  
  
  CONCLUSIONS
  Common polymorphisms on CYP3A4 and CYP3A5 genes do not modify the risk of developing digestive cancers in Western Europe.
authors.affiliation: Department of Pharmacology & Psychiatry, University of Extremadura, Badajoz, Spain. ggervasi@unex.es <ggervasi@unex.es>
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gervasini
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.forename: José M
authors.initials: JM
authors.lastname: Ladero
authors.forename: Rosa
authors.initials: R
authors.lastname: Pizarro
authors.forename: Javier
authors.initials: J
authors.lastname: Sastre
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Monserrat
authors.initials: M
authors.lastname: García
authors.forename: Manuel
authors.initials: M
authors.lastname: Diaz-Rubio
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012016:Reference Values; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: D003577:Cytochrome P-450 Enzyme System; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human