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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