fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2022-7-4-51-62fcmedicine-604Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL RESEARCHИммунологические и генетические предикторы рака молочной железыImmunological and genetic predictors of breast cancerhttps://orcid.org/0000-0002-8560-6719ГлушковА. Н.GlushkovA. N.

Глушков Андрей Николаевич, доктор медицинских наук, профессор, главный научный сотрудник лаборатории иммуногенетики 

650065, г. Кемерово, пр. Ленинградский, д. 10

Prof. Andrey N. Glushkov, MD, DSc, Professor, Chief Research Fellow, Laboratory of Immunogenetics, Institute of Human Ecology

10, Leningradsky Prospekt, Kemerovo, 650065

https://orcid.org/0000-0002-9368-2340ПоленокЕ. Г.PolenokE. G.

Поленок Елена Геннадьевна, кандидат фармацевтических наук, ведущий научный сотрудник лаборатории иммунохимии 

650065, г. Кемерово, пр. Ленинградский, д. 10

Dr. Elena G. Polenok, PhD, Leading Research Fellow, Laboratory of Immunochemistry, Institute of Human Ecology

10, Leningradsky Prospekt, Kemerovo, 650065

https://orcid.org/0000-0001-5870-7584ГордееваЛ. А.GordeevaL A.

Гордеева Людмила Александровна, кандидат биологических наук, ведущий научный сотрудник лаборатории иммуногенетики Института экологии человека 

650065, г. Кемерово, пр. Ленинградский, д. 10

Dr. Lyudmila A. Gordeeva, PhD, Leading Research Fellow, Laboratory of Immunogenetics, Institute of Human Ecology

10, Leningradsky Prospekt, Kemerovo, 650065

https://orcid.org/0000-0002-5530-3469МунС. А.MunS. A.

Мун Стелла Андреевна, кандидат медицинских наук, доцент, старший научный сотрудник лаборатории иммуногенетики 

650065, г. Кемерово, пр. Ленинградский, д. 10

Dr. Stella A. Mun, MD, PhD, Senior Research Fellow, Laboratory of Immunogenetics, Institute of Human Ecology

10, Leningradsky Prospekt, Kemerovo, 650065

 

stellamun@yandex.ruhttps://orcid.org/0000-0002-3405-6980ВоронинаЕ. Н.VoroninaE. N.

Воронина Елена Николаевна, кандидат биологических наук, старший научный сотрудник, заведующий группой молекулярной генетики 

630090, г. Новосибирск, пр. Академика Лаврентьева, д. 8

Dr. Elena N. Voronina, PhD, Senior Research Fellow, Chief of the Molecular Genetics Group

8, Akademika Lavrentieva Prospekt, Novosibirsk, 630090

https://orcid.org/0000-0003-0053-1752КостянкоМ. В.KostyankoM. V.

Костянко Михаил Владимирович, ведущий инженер кафедры органической химии Института фундаментальных наук

650000, г. Кемерово, ул. Красная, д. 6

Mr. Mikhail V. Kostyanko, Leading Engineer, Department of Organic Chemistry, Institute of Basic Sciences

6, Krasnaya Street, Kemerovo, 650000

https://orcid.org/0000-0003-0802-9759АнтоновА. В.AntonovA. V.

Антонов Александр Витальевич, заведующий отделением опухолей молочной железы

650036, г. Кемерово, ул. Волгоградская, д. 35

Dr. Alexander V. Antonov, MD, Chief of the Breast Cancer Unit

35, Volgogradskaya Street, Kemerovo, 650036

 

https://orcid.org/0000-0003-3860-825XВержбицкаяН. Е.VerzhbitskayaN. E.

Вержбицкая Наталья Евгеньевна, кандидат медицинских наук, врач-патологоанатом патологоанатомического отделения

650036, г. Кемерово, ул. Волгоградская, д. 35

Dr. Natalia E. Verzhbitskaya, MD, PhD, Chief of the Department of Pathology

35, Volgogradskaya Street, Kemerovo, 650036

КолпинскийГ. И.KolpinskiyG. I.

Колпинский Глеб Иванович, доктор медицинских наук, профессор кафедры лучевой диагностики и лучевой терапии с курсом онкологии ФГБОУ ВО «Кемеровский государственный медицинский университет» ; главный врач ГАУЗ «Клинический консультативно-диагностический центр им. И.А. Колпинского» 

650056, г. Кемерово, ул. Ворошилова, д. 22а; 650066, г. Кемерово, пр. Октябрьский, д. 53/1

Prof. Gleb I. Kolpinskiy, MD, DSc, Professor, Department of Radiology, Radiotherapy and Oncology, Kemerovo State Medical University; Chief Executive Officer, Kemerovo Clinical Diagnostic Сenter

22а, Voroshilova Street, Kemerovo, 650056; 53/1, Oktyabr’sky Prospekt, Kemerovo, 650066

Институт экологии человека Федерального исследовательского центра угля и углехимии СО РАНРоссияFederal Research Center of Coal and Coal Chemistry of the Siberian Branch of the Russian Academy of SciencesRussian FederationФГБУН «Институт химической биологии и фундаментальной медицины СО РАН»РоссияInstitute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesRussian FederationФГБОУ ВО «Кемеровский государственный университет»,РоссияKemerovo State UniversityRussian FederationГБУЗ «Кузбасский клинический онкологический диспансер им. М.С. Раппопорта»РоссияKuzbass Clinical Oncology DispensaryRussian FederationФГБОУ ВО «Кемеровский государственный медицинский университет» Министерства здравоохранения Российской Федерации; ГАУЗ «Клинический консультативно-диагностический центр им. И.А. Колпинского»РоссияKemerovo State Medical University; Kemerovo Clinical Diagnostic СenterRussian Federation202229122022745162Copyright © Глушков А.Н., Поленок Е.Г., Гордеева Л.А., Мун С.А., Воронина Е.Н., Костянко М.В., Антонов А.В., Вержбицкая Н.Е., Колпинский Г.И., 20222022Глушков А.Н., Поленок Е.Г., Гордеева Л.А., Мун С.А., Воронина Е.Н., Костянко М.В., Антонов А.В., Вержбицкая Н.Е., Колпинский Г.И.Glushkov A.N., Polenok E.G., Gordeeva L.A., Mun S.A., Voronina E.N., Kostyanko M.V., Antonov A.V., Verzhbitskaya N.E., Kolpinskiy G.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/604Цель

Цель. Выявить предполагаемые ассоциации идиотипических антител класса А против бензо[а]пирена, эстрадиола и прогестерона (IgA1 -Bp, IgA1 -E2, IgA1 -Pg) в комбинации с антиидиотипическими антителами класса G к эстрадиолу и прогестерону (IgG2 -E2 и IgG2 - Pg), а также полиморфных вариантов генов CYP1A1, CYP1A2, CYP1B1, CYP17A1, CYP19A1, GSTM1, GSTT1, GSTM1 с раком молочной железы (РМЖ) I стадии.

Материалы и методы

Материалы и методы. Идиотипические и антиидиотипические антитела исследовали с помощью ELISA в сыворотке крови 240 здоровых женщин и 505 больных РМЖ I стадии. Генотипирование CYP1A1 (rs4646903), CYP1A2 (rs762551), CYP1B1 (rs1056836), CYP19A1 (rs2470152), GSTM1(del), GSTT1(del) и GSTP1 (rs1695) 530 здоровых женщин и 694 больных РМЖ I стадии проводили с помощью ПЦР в режиме реального времени.

Результаты

Результаты. Низкие значения индивидуальных соотношений IgA1 -Bp/IgA1 -Pg≤1 в комбинации с низкими уровнями IgG2 -E2≤4 и высокими уровнями IgG2 -Pg>2 были обнаружены в сыворотке крови 20,6% здоровых женщин и 4,5% больных РМЖ (p=0,006; OR=1,8) и у 6,4% против 18,3% соответственно (p<0,0001; OR=3,3). Эти два варианта были объединены и обозначены как проканцерогенный иммунологический фенотип. Выявленные ассоциации были характерными только для больных РМЖ с ER+ опухолями. Полиморфизм гена rs1695 GSTP1 оказался ассоциированным только с ERРМЖ (p=0,004; OR=1,56). Не было обнаружено никаких взаимосвязей между исследованными антителами и полиморфизмами в генах CYP и GST.

Заключение

Заключение. Проканцерогенный иммунологический фенотип и полиморфизм rs1695 GSTP1 можно рассматривать как независимые предикторы соответственно ER+ и ERРМЖ.

Aim

Aim. To investigate the associations of idiotypic IgA antibodies against benzo[a]pyrene, estradiol and progesterone (IgA1 -Bp, IgA1 -E2, and IgA1 - Pg) with the corresponding anti-idiotypic IgG antibodies to estradiol and progesterone (IgG2 -E2 and IgG2 -Pg) and with gene polymorphisms of CYP1A1, CYP1A2, CYP1B1, CYP17A1, CYP19A1, GSTM1, GSTT1, and GSTP1 in patients with stage 1 breast cancer.

 Materials and Methods

 Materials and Methods. Idiotypic and anti-idiotypic antibodies in the serum of 240 healthy women and 505 patients with stage 1 breast cancer were measured by enzyme-linked immunosorbent assay. Prevalence of CYP1A1 (rs4646903), CYP1A2 (rs762551), CYP1B1 (rs1056836), CYP19A1 (rs2470152), GSTM1(del), GSTT1(del), and GSTP1 (rs1695) polymorphisms in 530 healthy women and 694 patients with stage 1 breast cancer were determined by real-time polymerase chain reaction.

Results

Results. Low personal IgA1 -Bp/IgA1 -Pg < 1 and IgA1 -E2/IgA1 -Pg < 1 ratios in combination with low IgG2 -E2 ≤ 4 and high IgG2 -Pg > 2 levels were found in 20.6% of healthy women and in 4.5% of breast cancer patients (p < 0.0001; OR = 0.2). Low IgA1 -Bp/IgA1 -Pg and high IgA1 -E2/IgA1 -Pg ratios in combination with low IgG2 -E2 and high IgG2 - Pg levels were revealed in 7.4% of healthy women and 2.8% of breast cancer patients (p = 0.009; OR = 0.4). These two variants were integrated and marked as protective immunological phenotype. High IgA1 - Bp/IgA1 -Pg and high IgA1 -E2/IgA1 -Pg ratios combined with high IgG2 -Pg and high or low IgG2 -E2 levels were found in 17.2% of healthy women and27.2% of breast cancer patients (p = 0.006; OR = 1.8) and in 6.4% of healthy women and in 18.3% of breast cancer patients (p < 0.0001; OR = 3.3), correspondingly. These two variants were integrated and marked as pro-carcinogenic immunological phenotype. These associations were found only with estrogen receptor-positive (ER+) breast cancer. GSTP1 (rs1695) gene polymorphism was associated exclusively with estrogen receptor-negative (ER-) breast cancer (p = 0.004; OR = 1.56). No interrelations be tween immunological phenotypes and studied polymorphisms of CYP and GST genes have been found.

Conclusion

Conclusion. Pro-carcinogenic immunological phenotype and rs1695 gene polymorphism within the GSTP1 gene were independent predictors of ER+ and ER- breast cancer correspondingly.

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The authors declare that there are no conflicts of interest present.