title: Polymorphism of the ERalpha and CYP1B1 genes in endometrial cancer in a Polish subpopulation.
abstract: OBJECTIVE
  Metabolic activation of estrogens may play a role in endometrial carcinogenesis; and polymorphism of the genes (whose product is involved in this process) may be associated with the modulation of the risk of endometrial cancer. CYP1B1 plays a major role in the metabolism of estrogens, which must firstly bind their receptors, estrogen receptor alpha (ERalpha) or ER beta. In the present study we investigated the association of two polymorphisms of the CYP1B1 gene (Arg48Gly [142C > G] and Leu432Val [4326C > G]) and a polymorphism of the ERalpha gene (975C > G) as well as a combination between them with endometrial cancer occurrence.
  
  
  METHODS
  Genotypes were determined in DNA from peripheral blood lymphocytes of 100 endometrial cancer patients and 100 age- and ethnically-matched cancer-free controls by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR).
  
  
  RESULTS
  We found an association between endometrial cancer occurrence and the Arg48Arg (142C > C)-CYP1B1 variant (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.17-3.79) and the 975C > G -ERalpha gene polymorphism (OR 3.84; 95%CI 2.08-7.10). Gene-gene interaction between the Arg48Arg (142C > C) and Leu432Val (4326C > G) variants and between Arg48Gly (142C > G) -CYP1B1 and 975C > G -ERalpha as well as Gly48Gly (142G > G)-CYP1B1 and 975C > G-ERalpha increased the risk of endometrial cancer (OR 2.70; 95%CI 1.12-6.49; OR 2.52; 95%CI 1.04-6.11 and OR 3.62; 95%CI 1.27-10.30, respectively). Additionally interaction between the 975C > G-ERalpha and Leu432Leu (4326C > C)-CYP1B1 or Leu432Val (4326C > G)-CYP1B1 variants also increased the risk (OR 4.68; 95%CI 1.81-12.07 and OR 6.00; 95%CI 2.19-16.47, respectively).
  
  
  CONCLUSIONS
  The CYP1B1 and ERalpha genes may play a role in endometrial cancer and the Arg48Gly (142C > G) -CYP1B1 and 975C > G-ERalpha polymorphisms may be considered as independent, early diagnostic markers in this disease.
authors.affiliation: Department of Molecular Genetics, University of Lodz, Lodz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sliwinski
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Sitarek
authors.forename: Tomasz
authors.initials: T
authors.lastname: Stetkiewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Sobczuk
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D016889:Endometrial Neoplasms / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D011044:Poland; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1