ANTIBODIES TO BENZO[A]PYRENE, ESTRADIOL AND PROGESTERONE IN THE POSTMENOPAUSAL BREAST CANCER WOMEN

The identification of women who are at high risk of developing breast cancer plays a key role in chemoprevention of breast cancer selective estrogen receptor modulators. purpose: To study specific immune responses to chemical carcinogens and sex steroid hormones associated with breast cancer in postmenopausal women. material and methods. Serum IgA-antibodies specific to benzo[a]pyrene, estradiol and progesterone were studied in 203 non-smoking healthy women and 469 non-smoking breast cancer patients (125 with ER– and 344 with ER+) using semi-quantitative enzyme immunoassay. results. The low levels of all three antibodies were revealed in 53.2 % of healthy donors, in 47.2 % of breast cancer patients with ER– and in 40.7 % of patients with ER+. The high levels of all three antibodies were found in 12.3 %, 18.4 % and 26.5 % of cases, respectively. In the studied groups, the levels of antibodies to estradiol and progesterone were correlated with the levels of antibodies to benzo[a]pyrene (rs=0.54–0.7, p<0.0001). Conclusion. Immunoassay of antibodies to exogenous and endogenous antigens could be useful for determining risk of developing ER+ breast cancer and preventing administration of tamoxifen and others selective modulators of estrogen receptors. Active immunization against exogenous chemical carcinogens could increase the levels of antibodies to endogenous steroids, thus stimulating breast cancer.

1. Pisareva L.F., Choinzonov E.L., Gurina L.I., Odintsova I.N., Shoikhet Ya.N., Lazarev A.F., Yudin S.V., Kosykh N.E. Epidemiological research of cancer in the region of Siberia and Far East. Dal'nevostochnyi meditsinskii zhurnal. 2005; 1: 51-55. [in Russian]

2. Sestak I. Preventative therapies for healthy women at high risk of breast cancer. Cancer Manag Res. 2014 Oct 17; 6: 423-30. doi: 10.2147/CMAR.S55219.

3. Ghoussaini M., Fletcher O., Michailidou K., Turnbull C., Schmidt M.K., Dicks E., Dennis J., Wang Q., Humphreys M.K., Lucca-rini C., Baynes C., Conroy D., Maranian M., Ahmed S., Driver K., Johnson N., OrrN., dos Santos SilvaI., Waisfisz Q., Meijers-HeijboerH., Uit-terlindenA.G., RivadeneiraF. Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet. 2012 Jan 22; 44 (3): 312-8. doi: 10.1038/ng.1049.

4. ImjanitovE.N. Hereditary breast cancer. Prakticheskaja onkologija. 2010; 11 (4): 258-266 [in Russian]

5. BurdennyjA.M., Kazubskaja T.P., Braga Je.A., Nosikov V.V., Logi-nov V.I. Association of polymorphic markers of xenobiotic biotransformation genes with breast cancer in females residing in Moscow. Molekuljar-naja medicina. 2012; 5: 30-34 [in Russian]

6. Economopoulos K.P., Sergentanis T.N. Three polymorphisms in cytochrome P450 1B1 (CYP1B1) gene and breast cancer risk: a metaanalysis. Breast Cancer Res Treat. 2010 Jul; 122(2): 545-51. doi: 10.1007/s10549-009-0728-z.

7. Go R.E., Hwang K.A., Choi K.C. Cytochrome P450 1 family and cancers. J Steroid Biochem Mol Biol. 2015 Mar; 147: 24-30. doi: 10.1016/j.jsbmb.2014.11.003.

8. Brewster A.M., Jorgensen T.J., Ruczinski I., Huang H.Y., Hoffman S., Thuita L., Newschaffer C., Lunn R.M., Bell D., Helzlsouer K.J. Polymorphisms of the DNA repair genes XPD (Lys751Gln) and XRCC1 (Arg399Gln and Arg194Trp): relationship to breast cancer risk and familial predisposition to breast cancer. Breast Cancer Res Treat. 2006 Jan; 95 (1): 73-80. doi: 10.1007/s10549-005-9045-3.

9. Duell E.J., Millikan R.C., Pittman G.S., Winkel S., Lunn R.M., Tse C.K., Eaton A., Mohrenweiser H.W., Newman B., Bell D.A. Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol Biomarkers Prev. 2001 Mar; 10 (3): 217-22.

10. 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 May; 313 (2): 640-6. doi:10.1124/jpet.104.081034.

11. De BuckS.S., SchellenbergerM.T., Ensch C., Muller C.P. Effects of antibodies induced by a conjugate vaccine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone absorptive transport, metabolism, and proliferation of human lung cells. Int J Cancer. 2010 Aug 1; 127 (3): 513-20. doi: 10.1002/ijc.25073.

12. Cernohorska H., Klimesova S., Lepsa L., Jinoch P., Milcova A., Schmuczerova J., Topinca J., Labaj J. Influence of immunization with non-genotoxic PAH-KLH conjugates on the resistance of organisms exposed to benzo[a]pyrene. Mutat Res. 2012 Feb 18; 742 (1-2): 2-10. doi: 10.1016/j.mrgentox.2011.10.016.

13. KondakovaI.V., SpirinaL.V., Koval V.D., ShashovaE.E., Choin-zonov E.L., Ivanova E.V., Kolomiets L.A., Chernyshova A.L., Slonim-skaya E.M., Usynin E.A., Afanas'ev S.G. Chymotrypsin-like activity and subunit composition of proteasomes in human cancers. Mol. Biol. 2014; 48 (3): 444-451. [in Russian]

14. Grova N., Prodhomme E.J., Schellenberger M.T., Farinelle S., Muller C.P. Modulation of carcinogen bioavailability by immunization with benzo[a]pyrene-conjugate vaccine. Vaccine. 2009 Jun 24; 27 (31): 4142-51. doi: 10.1016/j.vaccine.2009.04.052.

15. 15 . Moolten F.L., Capparel N., Boger E. Reduction of respiratory tract binding of benzo(a)pyrene in mice by immunization. J Natl Cancer Inst. 1978 Nov; 61 (5): 1347-9.

16. Moolten F.L., Schreiber B., Rizzone A. Protection of mice against 7.12 dimethilbenz(a)anthracene induced skin tumors by immunization with fluorinated analog of carcinogen. Cancer Res. 1981 Feb; 41 (2): 425-9.

17. Peck R.M., Peck E.B. Inhibition of chemically induced neoplasia by immunization with an antigenic carcinogen-protein conjugate. Cancer Res. 1971 Nov; 31 (11): 1550-4.

18. Schellenberger M.T., Farinelle S., Willieme S., Muller C.P. Evaluation of adjuvants for a candidate conjugates vaccine against benzo[a] pyrene. Human Vaccines. 2011; 7: 166-173.

19. Silbart L.K., Keren D.F. Reduction of intestinal carcinogen absorption by carcinogen-specific immunity. Science. 1989 Mar 17; 243 (4897): 1462-4.

20. CaldwellB.V., TillsonS.A., EsberH., ThorneycroftI.H. Survival of tumors after immunization against oestrogens. Nature. 1971; 231 (5298): 118-9.

21. 21 . Rosenberg M., Amir D., Folman Y. The effects of active immunization against progesterone on plasma concentrations of total and free progesterone, estradiol-17beta and LH in the cyclic ewe. Theriogenology. 1987; 28 : 4 1 7-426.

22. Glushkov A.N., Polenok E.G., Anosova T.P., SavchenkoJa.A., Bakanova M.L., Minina V.I., Mun S.A., Larin S.A., Kostjanko M.V. Serum antibodies to benzo[a]pyrene and chromosomal aberrations in lymphocytes of peripheral blood in the workers of coal processing enterprise. Rossijskij immunologicheskij zhurnal. 2011; 5 (14): 39-44 [in Russian]

23. Glushkov A.N., Polenok E.G., Verzhbickaja N.E., Titov V.A., Vafin I.A., Ragozhina S.E. Antibodies to chemical carcinogenes and steroid hormones in lung cancer patients. Rossijskij immunologicheskij zhurnal. 2014; 8 (2): 219-227 [in Russian].

24. Galati R., Zijno A., Crebelli R., Falasca G., Tomei F., Iecher F., Carta R., Verdina A. Detection of antibodies to the benzo[a]pyrene diol epoxide-DNA adducts in sera from individuals exposed to low doses of polycyclic aromatic hydrocarbons. J Exp Clin Cancer Res. 2001 Sep; 20 (3): 359-64.

25. Ustinov V.A., Matveeva V.A., Kostyanko M.V., Glushkov A.N. Antibodies against benzo[a]pyrene in immunized mouse and lung cancer patients. Exp Oncol. 2013 Sep; 35 (3): 207-10.

26. Anosova T.P., Polenok E.G., Anosov M.P., Krasil'nikova K.S., Kostjanko M.V., Verzhbickaja N.E., Gurov E.A., Vafin I.A., Ragozhi-na S.E., Glushkov A.N. Antibodies to xenoand endobiotics in patients with breast cancer. Izvestija Samarskogo nauchnogo centra RAN. 2012; 5 (2): 440-443 [in Russian]

27. Glushkov A.N., Anosova T.P., Nebesnaja N.G., Zheleznova L.Ja. Isotypic features of antibodies to polycyclic aromatic hydrocarbons in patients with cancer of breast, stomach, colon and rectum. Jeksperimental'naja Onkologija. 1996; 18: 426-428 [in Russian]

28. GlushkovA., PolenokE., KostyankoM., AntonovA., VerzhbitskayaN., Vafin I., Ragozhina S. Postmenopausal breast cancer risk in relation to antibodies specific to benzo[a]pyrene, estradiol and progesterone. Iran J Cancer Prev. 2016 Apr 24; 9 (2): e4212. doi: 10.17795/ijcp-4212.

29. Glushkov A.N. Immunological disbalance in carcinogen-esis. Med Hypotheses. 2014 Aug; 83 (2): 166-71. doi: 10.1016/j.mehy.2014.05.003.

30. Hajian-Tilaki K. Receiver Operating Characteristic (ROC) Curve Analysis for Medical Diagnostic Test Evaluation. Caspian J Intern Med. 2013; 4 (2): 627-35.

31. Verdina A. Carcinogen-modified DNA and specific humoral immunity toward carcinogen-DNA adducts. Ann Ist Super Sanita. 2006; 42 (2): 189-94.