The goal of this study was to investigate the association between the polymorphic loci of genes IL1B (rs16944), IL1RN (rs4251961), IL6 (rs1800795, rs1800796, rs1554606), IL8 (rs4073), IL10 (rs1800896), and TNFA (rs1800629) and breast cancer in women. The DNA samples of 521 women with breast cancer and 267 women without oncological pathology were studied. The study showed that age, concomitant chronic morbidity, and polymorphism of the IL6 gene are risk factors in postmenopausal women. Allele –572C (OR = 5.68; 95% CI = [2.70–11.97], pcor < 0.001), and haplotype rs1800796[C]–rs1800795[G]–rs1554606[G] (OR = 5.31, 95% CI = [1.87 – 15.10], pcor = 0.002) of the IL6 gene were associated with breast cancer. No association of loci in IL1B (rs16944), IL1RN (rs4251961), IL8 (rs4073), IL10 (rs1800896), or TNFA (rs1800629) was associated with the risk of breast cancer. The obtained data indicate that the –572C allele of the IL6 gene is associated with susceptibility in postmenopausal women to breast cancer. Our results can be useful for an understanding of the molecular mechanisms of breast cancer.

Serum concentrations of estradiol (Es) and progesterone (Pg), Es, Pg and benzo[a]pyrene-specific IgA and IgG antibodies were studied in 227 postmenopausal healthy women (HW) and 639 breast cancer patients (BCP). The high individual Pg/Es ratio ( 5.0) was revealed in HW (54.6%) and BCP (26.4%, p 0.0001, OR = 0.3) marked as “hormonal balance”. The low Pg/Es (≤ 5.0) ratio was detected more frequently in BCP (OR = 3.3) marked as “hormonal imbalance”. The high Pg/Es ratio was more common in HW with protective immunological phenotype (IgA-Bp/IgA-Pg ≤ 1 and IgA-Es/IgA-Pg ≤ 1) than with procarcinogenic immunological phenotype (IgA-Bp/IgA-Pg 1 and IgA-IgA-Es/IgA-Pg 1): 78.8 vs 47.4%, p = 0.005. The same parameters for IgG-immunological phenotypes in HW were 73.3 and 48.6%, p = 0.002. The differences between IgA-immunological phenotypes were lowered (41.6 vs 24.4%, p 0.007), whereas between IgG-phenotypes it was absent in BCP. Thus, for the first time it was revealed the influence of immunological phenotypes based on antibodies specific to the environmental chemical carcinogens and endogenous steroid hormones on the hormonal balance in HW and its reduced effects in BCP.

Previous studies found some associations between immunoglobulin class A antibodies specific to benzo[a]pyrene (IgA-Bp), estradiol (IgA-Es) and progesterone (IgA-Pg) as well as breast cancer (BC) in females and lung cancer (LC) in males. It was suggested that such antibodies affect serum Es and Pg levels.Our study was aimed at revealing putative features of mutual effects of IgA-Bp, IgA-Es and IgA-Pg on serum Es and Pg level both in healthy and BC females as well as healthy and LC males.Serum levels of Es and Pg and IgA-Bp, IgA-Es and IgA-Pg were measured by ELISA in 190 nonsmoking healthy and 518 BC females as well as 312 smoking healthy and 196 LC males.It was found that healthy subjects vs cancer patients prominently differed by assessing individual Pg/Es ratios: healthy vs BC females had it set at 6.6 vs 2.9 (p 0.0001), respectively, whereas in healthy vs LC males it was at 5.2 vs 10.1 (p 0.0001), respectively.Individual Pg/Es ratio paralleled in healthy females with high vs low IgA-Bp/IgA-Pg 1.5 and IgA-Es/IgA-Pg 1.5 ratios (3.5 vs 9.7, p 0.0001). No T such associations were observed in BC patients. In addition, the lowest individual Pg/Es ratio in healthy males was found together with IgA-Es/ IgA-Pg 1.5 ratios accompanied with IgA-Bp/IgA-Pg ≤ 1.5 (2.9) and peaked in case of concurrently low IgA-Bp/IgA-Pg ≤ 1.5 and IgA-Es/IgA-Pg ≤ 1.5 (5.2, p = 0.005) or high IgA-Bp/IgA-Pg 1.5 and IgA-Es/IgA-Pg 1.5 (6.5, p = 0.002). In contrast, the lowest Pg/Es ratio (7.4) was revealed in LC patients simultaneously bearing high IgA-Bp/IgA-Pg 1.5 and low IgA-Es/IgA-Pg ≤ 1.5 ratios compared to simultaneously low ratios (11.3, p = 0.002).In conclusion, individual Pg/Es ratios depended on individual IgA-Bp/IgA-Pg and IgA-Es/IgA-Pg ratios. A cooperative influence of serum antibodies specific to environmental chemical carcinogens and endogenous steroids on hormone balance was featured both in healthy subjects as well as BC females and LC males.The data obtained may be useful while developing new strategies to cancer prevention: by using selective modulators of estrogen receptors and aromatase inhibitors as well as for development of anticancer vaccines.

The relationship between autoantibodies specific to estradiol (Es)/ progesterone (Pg) and the concentrations of these hormones in the blood serum of healthy women and breast cancer patients has been previously revealed.Purpose: to study the association between anti-idiotypic antibodies to Es and Pg and the concentrations of these hormones in postmenopausal healthy women and breast cancer patients.Material and Methods. The levels of Es and Pg in the blood serum of 206 healthy women and 480 breast cancer patients were studied using competitive enzyme immunoassay. The levels of autoantibodies to Es and Pg and appropriate antiidiotypic antibodies in the same serums were studied using non-competitive enzyme immunoassay.Results. The high personal ratio of hormones (Pg/Es >4.0) was associated with the low breast cancer risk (OR=0.3; р<0.0001), high individual ratio of specific antibodies (IgA-Pg1/IgA-Es1>1.0; р=0.004) and high individual ratio of anti-idiotypic antibodies (IgG-Pg2/IgG-Es2>1.0; p<0.001) in healthy women, but not in breast cancer patients.Conclusion. The association between anti-idiotypic antibodies of G class specific to Es/ Pg and hormonal status was revealed in healthy women but not in breast cancer patients. Further studies on the mechanisms of immunoregulation of carcinogenesis are needed.

Previous studies found some associations between immunoglobulin class A antibodies specific to benzo[a]pyrene (IgA-Bp), estradiol (IgA-Es) and progesterone (IgA-Pg) as well as breast cancer (BC) in females and lung cancer (LC) in males. It was suggested that such antibodies affect serum Es and Pg levels. Our study was aimed at revealing putative features of mutual effects of IgA-Bp, IgA-Es and IgA-Pg on serum Es and Pg level both in healthy and BC females as well as healthy and LC males. Serum levels of Es and Pg and IgA-Bp, IgA-Es and IgA-Pg were measured by ELISA in 190 nonsmoking healthy and 518 BC females as well as 312 smoking healthy and 196 LC males. It was found that healthy subjects vs cancer patients prominently differed by assessing individual Pg/Es ratios: healthy vs BC females had it set at 6.6 vs 2.9 (p 1.5 and IgA-Es/IgA-Pg > 1.5 ratios (3.5 vs 9.7, p 1.5 ratios accompanied with IgA-Bp/IgA-Pg ≤ 1.5 (2.9) and peaked in case of concurrently low IgA-Bp/IgA-Pg ≤ 1.5 and IgA-Es/IgA-Pg ≤ 1.5 (5.2, p = 0.005) or high IgA-Bp/IgA-Pg > 1.5 and IgA-Es/IgA-Pg > 1.5 (6.5, p = 0.002). In contrast, the lowest Pg/Es ratio (7.4) was revealed in LC patients simultaneously bearing high IgA-Bp/IgA-Pg > 1.5 and low IgA-Es/IgA-Pg ≤ 1.5 ratios compared to simultaneously low ratios (11.3, p = 0.002). In conclusion, individual Pg/Es ratios depended on individual IgA-Bp/IgA-Pg and IgA-Es/IgA-Pg ratios. A cooperative influence of serum antibodies specific to environmental chemical carcinogens and endogenous steroids on hormone balance was featured both in healthy subjects as well as BC females and LC males. The data obtained may be useful while developing new strategies to cancer prevention: by using selective modulators of estrogen receptors and aromatase inhibitors as well as for development of anticancer vaccines.

Previous studies reported some associations between IgA and IgG antibodies specific to benzo[a] pyrene (Bp), estradiol (Es) and progesterone (Pg), and breast cancer (BC) in postmenopausal women. Likewise, the individual ratios of these antibodies (IgA-Bp/IgA-Pg, IgG-Bp/IgG-Pg, IgG-Es/IgG-Pg, IgG-Es/IgG-Pg) were associated with BC. It was suggested that development of antibodies to chemical carcinogens and steroid hormones was determined by functional polymorphisms of cytokine genes. The purpose of this study was to identify the suggested associations of antibodies to Bp, Es, Pg, and their individual ratios to the following gene polymorphisms: IL1RN (rs4251961), IL1B (rs16944), IL6 (rs1800795, rs1800796, rs1554606), IL8 (rs4073), TNFA (rs1800629) and CD40 (rs6074022) detected in postmenopausal healthy women and BC patients.The serum IgA and IgG antibodies specific to Bp, Es and Pg were studied in 470 healthy women and 995 BC patients by non-competitive solid phase immunoassay. The conjugates of Bp, Es, Pg with bovine serum albumin were used as adsorbed antigen. The goat antibodies against human IgA or IgG conjugated with horseradish peroxidase were used for the detection of bound hapten-specific antibodies. Cytokine gene polymorphisms were analyzed by the real-time PCR.Associations between the studied antibodies and their ratios with the gene polymorphisms in IL1RN (rs4251961), IL6 (rs1800795), TNFA (rs1800629) and CD40 (rs6074022) were found in healthy women. Higher individual ratios of IgA-Bp/IgA-Pg (p = 0.0001), IgG-Bp/IgG-Pg (p < 0.0001), IgG-Es/IgG-Pg (p = 0.0003) were associated with the allele C gene IL1RN. The higher IgG-Es levels were more common in the persons with allele G gene IL6 (p = 0.007), and with C allele of CD40 gene (p = 0.005). The high IgA-Pg levels were associated with A allele gene of TNFA (p = 0.008). Associations of antibodies were found only with genes polymorphisms in CD40 (rs6074022) in BC patients. Higher IgG-Es levels were more common in persons with allele T gene CD40 (p = 0.007).In conclusion, we revealed the participation of cytokines in immune regulation of antibody genesis for environmental chemical carcinogens and endogenous steroid hormones in healthy women and BC patients. The future investigations of antibodies specific to Bp, Es and Pg combined with the analysis genes polymorphisms in cytokines will be useful for detection of the individual hormone-dependent cancer risks in humans.

Specific antibodies against estradiol (Es) and progesterone (Pg) are known to modulate blood serum concentrations of these hormones and their biological effects after immunization of animals. It was suggested that specific IgA-Es and IgA-Pg could influence on Es and Pg levels in human blood serum. The purpose of this study was to identify the suggested correlations between serum Es and Pg and specific IgA-Es and IgA-Pg in postmenopausal healthy women (HW) and breast cancer patients (BCP). The serum levels of Es, Pg, IgA-Es and IgA-Pg were studied in 226 HW and 633 BCP by means of solid-phase immunoassay. The following results were obtained. The levels of Es in BCP (0.25 nmol/l) were higher than in HW (0.16; р < 0.0001). The levels of Pg were lower (0.79 vs 0.87; р < 0.0001), and individual Pg/Es ratios were lower (3.19 vs 6.64; р < 0.0001). Individual IgA-Pg/IgA-Es ratios correlated with decrease of Es (rs = -0.15; p = 0.029), with increase in Pg (rs = 0.38; р < 0.0001), and with increased Pg/Es ratio (rs = 0.29; р < 0.0001) in healthy women. Similar correlations were determined in BCP (correspondingly: rs = -0.14, р < 0.001; rs = 0.1, р = 0.009; rs = 0.15, р < 0.0001). The decrease of Es and increase of Pg and Pg/Es in BCP were less significant than in HW: the a quotients in regression у = ах+b (y = hormones levels and x = antibodies levels) in BCP were 3 to 4-fold lower than in HW. These peciliarities of interrelations between hormones and specific antibody levels were revealed only in ER+/PR+ BCP but not in ER+/PR- and ER-/PR- BCP. In conclusion, we have confirmed a suggestion about participation of specific antibodies in regulation of steroids levels in human blood serum. The immune regulation of hormonal status was weakened in BCP.