Антиидиотипические антитела против эстрадиола и генетический полиморфизм эстрогеновых рецепторов α и β у больных раком молочной железы

Markers for identification of ER⁺/PR⁺ breast cancer (BC) risks and conversion of ER⁺/ER⁺ to ER^-/PR^- tumors are necessary for effective prevention and therapy of BC by the selective ER modifying drugs. Our purpose was to reveal the suggested associations of gene polymorphisms of ESR1 and ESR2 and antiidiotypic antibodies to estradiol (IgG₂-E2) with ER⁺/PR⁺ BC risk, and conversion of ER⁺/PR⁺ to ER-/PR- tumors and to study interrelations between gene variants of ESR and IgG₂-E2 in healthy women and BC patients. Polymorphic loci of ESR1 (rs2234693) and ESR2 (rs4986938) were studied by the real-time PCR in 370 healthy women and 1169 BC patients. ER and PR in the tumor tissues were detected by standard immunohistochemical techniques. Serum IgG₂-E2 were studied using non-competitive enzyme immunoassay. TT, TC and CC genotypes of ESR1 were revealed at the equal frequency in healthy women and stage I BC patients. GG homozygotes of ESR2 were detected rarely, but AA were more frequent in BC patients with ER⁺/PR⁺ tumors (stage I) than in healthy women (44.0% and 14.2% vs 52.7% and 8.4%, respectively; p = 0.005). Low levels of IgG₂-ES were revealed more rarely but high levels were detected more frequently in BC patients with ER⁺/PR⁺ tumors (stage I) than in healthy persons (39.8% vs 60.2%, and 58.0% vs 42.0%, respectively; p = 0.0002). Decreasing proportion of ER⁺/PR⁺ tumors and corresponding increase of ER-/PR- tumors from stage I to II–IV (71.7% to 58.9% and 13.9% to 23.1%; p = 0.006) were revealed only for the TC heterozygotes of ESR1. The same conversion of ER⁺/PR⁺ tumors to ER^-/PR^- was detected for the GG homozygotes of ESR2 (p = 0.004). A similar ER/PR changes were revealed in BC patients with high IgG₂-E2 levels (74.7% to 57.6% and 11.3%, to 25.0%, respectively, p < 0.0001). High and low IgG₂-E2 levels showed similar frequency at any genotypes of ESR1 and ESR2, either among healthy women, or in BC patients. ESR1-2 gene polymorphisms and serum IgG₂-E2 levels may be used as independent markers for prediction of ER⁺/PR⁺ breast cancer, and for assessment of ER⁺/PR⁺ to ER^-/PR^- tumor conversion during BC progression.

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