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

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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.

About the authors

Anton V. Averianov

Institute of Human Ecology, Federal Research Center of Coal and Coal Chemistry

Author for correspondence.
Email: Averianov_AV@mail.ru

Biological Engineer, Laboratory of Immunochemistry, Institute of Human Ecology, Federal Research Center of Coal and Coal Chemistry

Russian Federation, Kemerovo

Alexander V. Antonov

Kuzbass Clinical Oncology Dispensary

Email: al0412@mail.ru

Head, Department No. 5, Kuzbass Clinical Oncology Dispensary

Russian Federation, Kemerovo

Alexey S. Zhivotovskiy

Kuzbass Clinical Oncology Dispensary

Email: Zhivotovskii@mail.ru

PhD (Medicine), Head, Department No. 6, Kuzbass Clinical Oncology Dispensary

Russian Federation, Kemerovo

Mikhail V. Kostyanko

Kemerovo State University

Email: ihe@list.ru

Leading Engineer, Department of Organic and Physical Chemistry, Kemerovo State University

Russian Federation, Kemerovo

Ilgiz A. Vafin

Kuzbass Center of Blood

Email: ihe@list.ru

Chief Physician, Kuzbass Center of Blood

Russian Federation, Kemerovo

Gleb I. Kolpinskiy

Kuzbass Clinical Diagnostic Center

Email: glebss@mail.ru

Chief Physician, Kuzbass Clinical Diagnostic Center

Russian Federation, Kemerovo

Andrey N. Glushkov

Institute of Human Ecology, Federal Research Center of Coal and Coal Chemistry

Email: ihe@list.ru

PhD, MD (Medicine), Professor, Director, Institute of Human Ecology, Federal Research Center of Coal and Coal Chemistry

Russian Federation, Kemerovo

References

  1. Глушков А.Н., Поленок Е.Г., Гордеева Л.А., Мун С.А., Костянко М.В., Антонов А.В., Титов В.А., Вержбицкая Н.Е., Вафин И.А. Иммунологический дисбаланс при раке молочной железы и раке легкого у женщин в постменопаузе // Медицинская иммунология, 2018. Т. 20, № 6. С. 139-146. [Glushkov A.N., Polenok E.G., Gordeeva L.A., Moon S.A., Kostyanko M.V., Antonov A.V., Titov V.A., Verzhbitskaya N.E., Vafin I.A. Immunological imbalance in breast and lung cancer in postmenopausal women. Meditsinskaya immunologiya = Medical Immunology (Russia), 2018, Vol. 20, no. 6, pp. 139-146. (In Russ.)] doi: 10.15789/1563-0625-2018-6-927-934.
  2. Глушков А.Н., Поленок Е.Г., Мун С.А., Гордеева Л.А., Костянко М.В., Луценко В.А., Колпинский Г.И. Индивидуальный иммунологический фенотип и гормональный баланс у женщин в постменопаузе // Российский иммунологический журнал, 2020. Т. 23, № 1. С. 61-68. [Glushkov A.N., Polenok E.G., Moon S.A., Gordeeva L.A., Kostyanko M.V., Lutsenko V.A., Kolpinsky G.I. Individual immunological phenotype and hormonal balance in postmenopausal women. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2020, Vol. 23, no. 1, pp. 61-68. (In Russ.)]
  3. Злокачественные новообразования в России в 2019 году (заболеваемость и смертность). М.: Гельветика, МНИОИ им. П.А. Герцена, 2020. [Электронный ресурс]. Режим доступа: https://glavonco.ru/cancer_register/Забол_2019_Электр.pdf. [Malignant neoplasms in Russia in 2019 (morbidity and mortality)]. Moscow: Helvetika, P. Herzen Research Institute of Oncology, 2020. [Electronic resource]. Access mode: https://glavonco.ru/cancer_register/Забол_2019_Электр.pdf.
  4. Худолей В.В. Канцерогены: характеристики, закономерности, механизмы действия. СПб.: НИИ химии СПбГУ, 1990. 419 с. [Khudoley V.V. Carcinogens: characteristics, patterns, mechanisms of action. St. Petersburg: Research Institute of Chemistry]. St. Petersburg: Research Institute of Chemistry, St. Petersburg State University, 1990. 419 p.
  5. Agudo A., Peluso M., Munnia A., Luján-Barroso L., Barricarte A., Amiano P., Navarro C., Sánchez M.-J., Quirós J.R., Ardanaz E. Aromatic DNA adducts and breast cancer risk: a case-cohort study within the EPIC-Spain. Carcinogenesis, 2017, Vol. 38, Iss. 7, pp. 691-698.
  6. de Buck S.S., Augustijns P., Muller C.P. Specific antibody modulates absorptive transport and metabolic activation of benzo[a]pyrene across Caco-2 monolayers. J. Pharmacol. Exp. Ther., 2005, Vol. 313, no. 2, pp. 640-646.
  7. Glushkov A.N., Polenok E.G., Mun S.A., Gordeeva L.A. Inversion of natural immuno-hormonal interactions under influence of antibodies against environmental chemical carcinogens. Med. Hypotheses, 2020, Vol. 144, 109981. doi: 10.1016/j.mehy.2020.109981.
  8. Gunter M.J., Divi R.L., Kulldorff M., Vermeulen R., Haverkos K.J., Kuo M.M., Strickland P., Poirier M.C., Rothman N., Sinha R.. Leukocyte polycyclic aromatic hydrocarbon-DNA adduct formation and colorectal adenoma. Carcinogenesis, 2007, Vol. 28, no. 7, pp. 1426-1429.
  9. Hajian-Tilaki K. Receiver Operating Characteristic (ROC) curve analysis for medical diagnostic test evaluation. Caspian J. Intern. Med., 2013, Vol. 4, no. 2, pp. 627-635.
  10. Harris D.L., Washington M.K., Hood D.B., Roberts L.J. II, Ramesh A. Dietary fat-influenced development of colon neoplasia in ApcMin mouse exposed to benzo(a)pyrene. Toxicol. Pathol., 2009, Vol. 37, no. 7, pp. 938-946.
  11. Hogan A.M., Collins D., Baird A.W., Winter D.C. Estrogen and gastrointestinal malignancy. Mol. Cell. Endocrinol., 2009, Vol. 307, no. 1-2, pp. 19-24.
  12. Jamin E.L., Riu A., Douki T., Debrauwer L., Cravedi J-P., Zalko D., Audebert M.. Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis. PLoS One, 2013, Vol. 8, no. 3. doi: 10.1371/journal.pone.0058591.
  13. Mohammed H., Russell I.A., Stark R., Rueda O.M., Hickey T.E., Tarulli G.A., Serandour A.A., Birrell S.N., Bruna A., Saadi A., Menon S., Hadfield J., Michelle Pugh M., Raj G.V., Brown G.B., D’Santos C., Robinson J.L.L., Silva G., Launchbury R., Perou C.M., Sting J., Caldas C., Tilley W.D., Carroll J.S. Progesterone receptor modulates ERα action in breast cancer. Nature, 2015, Vol. 523, no. 7560, pp. 313-317.
  14. Rawlings N.C., Kennedy S.W., Henricks D.M. The active immunization of the cyclic ewe against an estrone protein conjugate. Theriogenology, 1979, Vol. 12, no. 3, pp. 139-151.
  15. Santen R.J., Yue W., Wang J-P. Estrogen metabolites and breast cancer. Steroids, 2015, Vol. 99, Pt A, pp. 61-66.
  16. Sasso C.S., Santiano F.E., Arboccó F.C.V., Zyla L.E., Semino S.N., Guerrero-Gimenez M.E., Creydt V.P., Fontana C.M.L., Carón R.W. Estradiol and progesterone regulate proliferation and apoptosis in colon cancer. Endocr. Connect., 2019, Vol. 8, no. 3, pp. 217-229.
  17. Yu F.-L. 17β-Estradiol epoxidation as the molecular basis for breast cancer initiation and prevention. Asia Pacific J. Clin. Nutr., 2002, Vol. 11, Suppl. 7, pp. 460-466.

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Copyright (c) 2022 Averianov A.V., Antonov A.V., Zhivotovskiy A.S., Kostyanko M.V., Vafin I.A., Kolpinskiy G.I., Glushkov A.N.

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