Aim: 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.