Incidence of IgA antibodies specific to benzo[a]pyrene and steroid hormones in women with colorectal cancer and breast cancer

A. V. Averianov, A. Antonov, Alexey S. Zhivotovskiy, M. Kostyanko, I. Vafin, G. Kolpinskiy, A. Glushkov
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Abstract

Formation of DNA adducts of chemical carcinogens is a trigger for carcinogenesis. Adducts of benzo[a]pyrene metabolites and estradiol metabolites with DNA have been found in normal and tumor cells in healthy women and patients with breast and colorectal cancer. These low-weight compounds in macromolecular complexes induce the synthesis of specific antibodies. Previously, the presence of specific antibodies against benzo[a]pyrene (IgA-Bp), estradiol (IgA-Es) and progesterone (IgA-Pg) was revealed in breast cancer patients. The aim of this study is to identify the putative features of the IgA-Bp, IgA-Es, and IgA-Pg formation in postmenopausal women with colorectal cancer, in comparison with healthy and breast cancer patients. Using a noncompetitive enzyme-linked immunosorbent assay, the content of these antibodies was studied in the blood serum of healthy women (n = 401), patients with colorectal cancer (n = 219) and breast cancer (n = 1469) using conjugates of Bp, Es, and Pg with bovine serum albumin as adsorbed antigens. When compared with healthy people, the patients with colorectal cancer exhibited higher incidence of IgA-Bp 3 (75% vs 37%, p 0.0001, OR = 5.0), as well as more common levels of individual antibody ratios: IgA-Bp/IgA-Es 1 (82% vs 41%, p 0.0001, OR = 6.5); IgA-Bp/IgA-Pg 1.5 (77% vs 20%, p 0.0001, OR = 13.4); IgA-Es/IgA-Pg 1 (89% vs 48%, p 0.0001, OR = 8.7). In breast cancer patients, compared with healthy people, high IgA-Bp values ( 3) were more common (45% vs 37%, p 0.004, OR = 1.4), as well as increased IgA-Bp/IgA-Es ratio 1 (57% vs 41%, p 0.0001, OR = 1.9), IgA-Bp/IgA-Pg 1.1 (71% vs 36%, p 0.0001, OR = 4.4) and IgA-Es/IgA-Pg 1.1 (71% vs 41%, p 0.0001, OR = 3.5). In patients with colorectal cancer, compared with patients with breast cancer we have found higher incidence of increased IgA-Bp values ( 3) (75% vs 45%, p 0.0001), IgA-Es 3 (53% vs 39%, p 0, 0001), and of IgA-Pg 2 (52% vs 44%, p = 0.025), as well as IgA-Bp/IgA- Es 1 (82% vs 57%, p 0.0001, OR = 50.8 ); IgA-Bp/IgA-Pg 1.5 (77% vs 49%, p 0.0001); IgA-Es/IgA-Pg 1.1 (85% vs 71%, p 0.0001). The apparently high serum IgA-Bp levels reflect the formation of DNA-Bp adducts at large scale in target cells in colorectal cancer compared with healthy women and breast cancer patients, due to direct exposure of colon epithelium to Bp from food. Immunoassay for IgA-Bp, IgA-Es and IgA-Pg is proposed for assessing individual risk of colorectal cancer in postmenopausal women. The ratios of IgA Bp/IgA-Pg levels 1.5 represent the most informative marker of individual risk for colorectal cancer.
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结直肠癌和乳腺癌女性中苯并[a]芘和类固醇激素特异性IgA抗体的发生率
化学致癌物DNA加合物的形成是致癌的诱因。在健康妇女以及乳腺癌和结直肠癌患者的正常细胞和肿瘤细胞中发现了苯并[a]芘代谢物和雌二醇代谢物与DNA的加合物。这些在大分子复合物中的低质量化合物诱导特异性抗体的合成。此前,在乳腺癌患者中发现了针对苯并[a]芘(IgA-Bp)、雌二醇(IgA-Es)和黄体酮(IgA-Pg)的特异性抗体。本研究的目的是确定绝经后结直肠癌妇女中IgA-Bp、IgA-Es和IgA-Pg形成的推定特征,并与健康和乳腺癌患者进行比较。采用非竞争性酶联免疫吸附法,研究了健康女性(401)、结直肠癌患者(219)和乳腺癌患者(1469)血清中这些抗体的含量,将Bp、Es和Pg与牛血清白蛋白结合作为吸附抗原。与健康人群相比,结直肠癌患者表现出更高的IgA-Bp 3发病率(75% vs 37%, p 0.0001, OR = 5.0),以及更常见的个体抗体比率水平:IgA-Bp/IgA-Es 1 (82% vs 41%, p 0.0001, OR = 6.5);IgA-Bp/IgA-Pg 1.5 (77% vs 20%, p 0.0001, OR = 13.4);IgA-Es/IgA-Pg 1 (89% vs 48%, p 0.0001, OR = 8.7)。在乳腺癌患者中,与健康人群相比,高IgA-Bp值(3)更为常见(45% vs 37%, p 0.004, OR = 1.4), IgA-Bp/IgA-Es比值1 (57% vs 41%, p 0.0001, OR = 1.9)、IgA-Bp/IgA-Pg 1.1 (71% vs 36%, p 0.0001, OR = 4.4)和IgA-Es/IgA-Pg 1.1 (71% vs 41%, p 0.0001, OR = 3.5)升高。在结直肠癌患者中,与乳腺癌患者相比,我们发现IgA- bp值升高的发生率更高(3)(75% vs 45%, p 0.0001), IgA-Es 3 (53% vs 39%, p 0.0001), IgA- pg 2 (52% vs 44%, p = 0.025),以及IgA- bp /IgA- Es 1 (82% vs 57%, p 0.0001, OR = 50.8);IgA-Bp/IgA-Pg 1.5 (77% vs 49%, p 0.0001);IgA-Es/IgA-Pg 1.1 (85% vs 71%, p 0.0001)。与健康女性和乳腺癌患者相比,结直肠癌患者血清中IgA-Bp水平明显升高,反映了结肠癌患者的靶细胞中DNA-Bp加合物的大规模形成,这是由于结肠上皮直接暴露于食物中的Bp。IgA-Bp、IgA-Es和IgA-Pg的免疫测定被建议用于评估绝经后妇女结直肠癌的个体风险。IgA Bp/IgA- pg水平的比值为1.5,是个体结直肠癌风险的最有信息的标志。
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