akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2023.463akusherstvo-1865Research ArticleОRIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИAn interplay between genes SLCO1B1, NR2F2, JMJD1C and obesity in developing breast cancerРоль взаимодействий генов SLCO1B1, NR2F2, JMJD1C и ожирения при развитии рака молочной железыhttps://orcid.org/0009-0002-0689-4917ПасеновК. Н.PasenovK. N.

Пасенов Константин Николаевич – аспирант кафедры медико-биологических дисциплин медицинского института

308015 Белгород, ул. Победы, д. 85

Konstantin N. Pasenov – MD, Postgraduate Student, Department of Medical and Biological Disciplines, Medical Institute

85 Pobedy Str., Belgorod 308015

https://orcid.org/0000-0002-5652-0166ПономаренкоИ. В.PonomarenkoI. V.

Пономаренко Ирина Васильевна – д.м.н., доцент кафедры медико-биологических дисциплин. Scopus Author ID: 57190225823

308015 Белгород, ул. Победы, д. 85

Irina V. Ponomarenko – MD, Dr Med Sci, Associate Professor, Department of Medical and Biological Disciplines, Medical Institute. Scopus Author ID: 57190225823

85 Pobedy Str., Belgorod 308015

https://orcid.org/0000-0003-1254-6134ЧурносовМ. И.ChurnosovM. I.

Чурносов Михаил Иванович – д.м.н., профессор, зав. кафедрой медико-биологических дисциплин. Scopus Author ID: 6601948788

308015 Белгород, ул. Победы, д. 85

Mikhail I. Churnosov – MD, Dr Med Sci, Professor, Head of the Department of Medical and Biological Disciplines, Medical Institute. Scopus Author ID: 6601948788

85 Pobedy Str., Belgorod 308015

churnosov@bsu.edu.ruФГАОУ ВО «Белгородский государственный национальный исследовательский университет»РоссияBelgorod National Research UniversityRussian Federation2024251220231813545Copyright © Pasenov K.N., Ponomarenko I.V., Churnosov M.I., 20242024Пасенов К.Н., Пономаренко И.В., Чурносов М.И.Pasenov K.N., Ponomarenko I.V., Churnosov M.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/1865Aim

Aim: to evaluate a role of polymorphic variants rs4149056 SLCO1B1, rs8023580 NR2R2 and rs7910927 JMJD1C in developing obesity-related female breast cancer (BC).

Materials and Methods

Materials and Methods. A retrospective comparative study was performed on a sample of 1,498 women (358 BC patients and 1,140 control subjects) stratified into 2 groups based on verified obesity: obese (119 BC patients and 253 control subjects) and non-obese (239 BC patients and 887 control subjects). Genotyping of three single nucleotide polymorphisms (SNP) – rs7910927 JMJD1C, rs8023580 NR2F2, rs4149056 SLCO1B1 was performed to be further analyzed separately in each group of obese and non-obese women for associations of such loci and interplay with breast cancer.

Results

Results. Polymorphisms rs8023580 NR2F2, rs4149056 SLCO1B1 and rs7910927 JMJD1C are not independently associated with BC in obese and non-obese women, whereas their interlocus interactions are BC-significant in each of the examined groups (pperm = 0.047 and pperm = 0.0012, respectively). Among obese women, the combination of TC-TT-GG genotypes (for rs8023580–rs4149056–rs7910927) is associated with a low risk of developing BC (β = –2.45), whereas the combination of TC-TC-GG genotypes is associated with increased BC risk (β=1.42). In non-obese women, a combination of the TC-TT-GT genotypes (β = –0.47) has a protective effect on the BC occurrence, and the risk effect is coupled to TC-TC-GT (β = 0.91) and TC-CC-GT (β = 1.45). The appearance of allele C rs4149056 in female genotype and its increased "concentration" results in higher BC risk.

Conclusion

Conclusion. The allele variant C rs4149056 in the interlocus interactions between the SLCO1B1, NR2F2 and JMJD1C genes is a "universal" factor that elevates BC risk in both obese and non-obese women. The genotype GG rs7910927 is BC-significant in interlocus interactions in obese women, whereas in non-obese women it is coupled to the genotype GT rs7910927.

Цель

Цель: оценить роль полиморфных вариантов rs4149056 SLCO1B1, rs8023580 NR2F2 и rs7910927 JMJD1C при развитии рака молочной железы (РМЖ) у женщин в зависимости от наличия/отсутствия ожирения.

Материалы и методы

Материалы и методы. Выполнено ретроспективное сравнительное исследование на выборке из 1498 женщин (358 больных РМЖ и 1140 контроля), которые в зависимости от наличия/отсутствия ожирения были разделены на 2 группы: с ожирением (119 больных РМЖ и 253 контроля) и без ожирения (239 больных РМЖ и 887 контроля). Выполнено генотипирование 3 однонуклеотидных полиморфизмов (англ. single nucleotide polymorphism, SNP) – rs7910927 JMJD1C, rs8023580 NR2F2, rs4149056 SLCO1B1 и проведен анализ ассоциаций этих локусов и их взаимодействий с РМЖ отдельно в каждой группе женщин – с ожирением и без ожирения.

Результаты

Результаты. Полиморфизмы rs8023580 NR2F2, rs4149056 SLCO1B1 и rs7910927 JMJD1C самостоятельно не ассоциированы с РМЖ у женщин как с ожирением, так и без ожирения, тогда как их межлокусные взаимодействия являются РМЖ-значимыми в каждой из этих групп женщин (pperm = 0,047 и pperm = 0,0012 соответственно). Среди женщин с ожирением комбинация генотипов ТС-ТТ-GG (для rs8023580–rs4149056–rs7910927) связана с низким риском развития РМЖ (β = –2,45), а комбинация генотипов ТС-ТС-GG ассоциирована с повышенным риском возникновения заболевания (β = 1,42). У женщин без ожирения защитное действие на возникновение РМЖ имеет комбинация генотипов ТС-ТТ-GТ (β = –0,47), а рисковое влияние – ТС-ТС-GТ (β = 0,91) и ТС-СС-GТ (β = 1,45). Появление в генотипе женщины аллеля С rs4149056 и увеличение его «концентрации» приводит к повышению риска возникновения заболевания.

Заключение

Заключение. Аллельный вариант С rs4149056 при межлокусных взаимодействиях генов SLCO1B1, NR2F2 и JMJD1C является «универсальным» фактором, повышающим риск развития РМЖ как у женщин с ожирением, так и без ожирения. Генотип GG rs7910927 является РМЖ-значимым в межлокусных взаимодействиях у женщин с ожирением, а у женщин без ожирения таковым является генотип GТ rs7910927.

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