DOI: 10.18413/2658-6533-2023-9-4-0-9

Comorbidity and syntropy of benign proliferative diseases of the female reproductive system: non-genetic, genetic, and epigenetic factors (review)

Marina S. Ponomarenko
Evgeny A. Reshetnikov
Maria M. Churnosova
Yuliya N. Reshetnikova
Vladimir I. Churnosov
Irina V. Ponomarenko

Background: Benign proliferative diseases of the female reproductive system (endometriosis, endometrial hyperplasia, and uterine leiomyoma) are comorbid and often occur together. The aim of the study: To establish common risk factors for the development of benign proliferative diseases of the female reproductive system (endometriosis, endometrial hyperplasia, and uterine leiomyoma). Materials and methods: The review includes up-to-date data from articles found in PubMed and Elibrary on this topic. Results: The article reviews the recent literature about factors determining comorbidity and syntropy of the diseases. Their comorbidity may be based on common environmental risk factors (early menarche, body mass index, induced abortions, etc.) and mechanisms of the pathogenesis, which include hormone-dependent cellular proliferation associated with the action of sex hormones and hormone-independent cellular proliferation processes stimulated by growth factors and cytokines, apoptosis, and pathological neoangiogenesis, etc. These common mechanisms are backed by syntropic genes (e.g., FSHB, COMT). Syntropy and pleiotropy appear to be closely related: syntropic genes manifest pleiotropic effects too. Also, epigenetic factors, such as miRNAs are important determinants of the diseased phenotypes. Conclusion: Identification of the shared factors contributing to the benign proliferative diseases of the female reproductive system helps to determine targets for therapeutic intervention and efficient control of the comorbidity.

Keywords: uterine leiomyoma, endometriosis, endometrial hyperplasia, comorbidity, syntropy.

Number of views: 480 (view statistics)

Количество скачиваний: 650

Full text (HTML)Full text (PDF)To articles list

Information for citation:

Ponomarenko MS, Reshetnikov EA, Churnosova MM, et al. Comorbidity and syntropy of benign proliferative diseases of the female reproductive system: non-genetic, genetic, and epigenetic factors (review). Research Results in Biomedicine. 2023;9(4):544-556. DOI: 10.18413/2658-6533-2023-9-4-0-9

User comments
Reference lists

While nobody left any comments to this publication.
You can be first.

Wise LA, Laughlin-Tommaso SK. Epidemiology of uterine fibroids: from menarche to menopause. Clinical Obstetrics and Gynecology. 2016;59(1):2-24. DOI: https://doi.org/10.1097/GRF.0000000000000164
Sanderson PA, Critchley HOD, Williams ARW, et al. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Human Reproduction Update. 2017;23(2):232-254. DOI: https://doi.org/10.1093/humupd/dmw042
Laganà AS, Garzon S, Götte M, et al. The pathogenesis of endometriosis: molecular and cell biology insights. International Journal of Molecular Sciences. 2019;20(22):5615. DOI: https://doi.org/10.3390/ijms20225615
Commandeu AE, Styer AK, Teixeira JM. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth. Human Reproduction Update. 2015;21(5):593-615. DOI: https://doi.org/10.1093/humupd/dmv030
Backonja U, Louis GMB, Lauver DR. Overall adiposity, adipose tissue distribution, and endometriosis: a systematic review. Nursing Research. 2016;65(2):151-166. DOI: https://doi.org/10.1097/NNR.0000000000000146
Treloar SA, O'Connor DT, O'Connor VM, et al. Genetic influences on endometriosis in an Australian twin sample. Fertility and Sterility. 1999;71(4):701-710. DOI: https://doi.org/10.1016/S0015-0282(98)00540-8
Chandra V, Kim JJ, Benbrook DM, et al. Therapeutic options for management of endometrial hyperplasia. Journal of Gynecologic Oncology. 2016;27(1):e8. DOI: https://doi.org/10.3802/jgo.2016.27.e8
Epplein M, Reed SD, Voigt LF, et al. Risk of complex and atypical endometrial hyperplasia in relation to anthropometric measures and reproductive history. American Journal of Epidemiology. 2008;168(6):563-576. DOI: https://doi.org/10.1093/aje/kwn168
Nezhat C, Li A, Abed S, et al. Strong association between endometriosis and symptomatic leiomyomas. Journal of the Society of Laparoendoscopic Surgeons. 2016;20(3):e2016.00053. DOI: https://doi.org/10.4293/JSLS.2016.00053
Geethamala K, Murthy VS, Vani BR, et al. Uterine Leiomyomas: An ENIGMA. Journal of Mid-Life Health. 2016;7(1):22-27. DOI: https://doi.org/10.4103/0976-7800.179170
Ponomarenko I, Reshetnikov E, Polonikov A, et al. Candidate genes for age at menarche are associated with endometrial hyperplasia. Gene. 2020;757:144933. DOI: https://doi.org/10.1016/j.gene.2020.144933
Ponomarenko I, Reshetnikov E, Polonikov A, et al. Candidate genes for age at menarche are associated with endometriosis. Reproductive BioMedicine Online. 2020;41(5):943-956. DOI: https://doi.org/10.1016/j.rbmo.2020.04.016
Song L, Shen L, Mandiwa C, et al. Induced and spontaneous abortion and risk of uterine fibroids. Journal of Women's Health. 2017;26(1):76-82. DOI: https://doi.org/10.1089/jwh.2016.5913
Ross RK, Pike MC, Vessey MP, et al. Risk factors for uterine fibroids: reduced risk associated with oral contraceptives. British Medical Journal (Clinical research ed.). 1986;293:359-362. DOI: https://doi.org/10.1136/bmj.293.6543.359
Luoto R, Kaprio J, Rutanen EM, et al. Heritability and risk factors of uterine fibroids--the Finnish Twin Cohort study. Maturitas. 2000;37(1):15-26. DOI: https://doi.org/10.1016/s0378-5122(00)00160-2
Moini A, Malekzadeh F, Amirchaghmaghi E, et al. Risk factors associated with endometriosis among infertile Iranian women. Archives of Medical Science. 2013;9(3):506-514. DOI: https://doi.org/10.5114/aoms.2013.35420
Liu Y, Zhang W. Association between body mass index and endometriosis risk: a meta-analysis. Oncotarget. 2017;8(29):46928-46936. DOI: https://doi.org/10.18632/oncotarget.14916
Nnoaham KE, Webster P, Kumbang J, et al. Is early age at menarche a risk factor for endometriosis? A systematic review and meta-analysis of case-control studies. Fertility and Sterility. 2012;98(3):702-712.e6. DOI: https://doi.org/10.1016/j.fertnstert.2012.05.035
Ponomarenko I, Reshetnikov E, Altuchova O, et al. Association of genetic polymorphisms with age at menarche in Russian women. Gene. 2019;686:228-236. DOI: https://doi.org/10.1016/j.gene.2018.11.042
Alsudairi HN, Alrasheed AT, Dvornyk V. Estrogens and uterine fibroids: an integrated view. Research Results in Biomedicine. 2021;7(2):156-163. DOI: https://doi.org/10.18413/2658-6533-2021-7-2-0-6
Douglas NI, Pavlova TU, Burtseva TE, et al. Women's reproductive health in the Sakha Republic (Yakutia). International Journal of Circumpolar Health. 2014;73(1):25872. DOI: https://doi.org/10.3402/ijch.v73.25872
Schneider AP, 2nd Zainer CM, Kubat CK, et al. The breast cancer epidemic: 10 facts. The Linacre quarterly. 2014;81(3):244-277. DOI: https://doi.org/10.1179/2050854914Y.0000000027
Vikhlyaeva EM, Khodzhaeva ZS, Fantschenko ND. Familial predisposition to uterine leiomyomas. International Journal of Gynecology and Obstetrics. 1995;51(2):127-131. DOI: https://doi.org/10.1016/0020-7292(95)02533-I
Adachi S, Tajima A, Quan J, et al. Meta-analysis of genome-wide association scans for genetic susceptibility to endometriosis in Japanese population. Journal of Human Genetics. 2010;55:816-821. DOI: https://doi.org/10.1038/jhg.2010.118
Albertsen HM, Chettier R, Farrington P, et al. Genome-wide association study link novel loci to endometriosis. PLoS ONE. 2013;8(3):e58257. DOI: https://doi.org/10.1371/journal.pone.0058257
Nyholt DR, Low SK, Anderson CA, et al. Genome-wide association meta-analysis identifies new endometriosis risk loci. Nature Genetics. 2012;44:1355-1359. DOI: https://doi.org/10.1038/ng.2445
Painter JN, Anderson CA, Nyholt DR, et al. Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nature Genetics. 2011;43:51-54. DOI: https://doi.org/10.1038/ng.731
Uimari O, Rahmioglu N, Nyholt DR, et al. Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis. Human Reproduction. 2017;32(4):780-793. DOI: https://doi.org/10.1093/humrep/dex024
Uno S, Zembutsu H, Hirasawa A, et al. A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. Nature Genetics. 2010;42:707-710. DOI: https://doi.org/10.1038/ng.612
Sapkota Y, Steinthorsdottir V, Morris AP, et al. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nature Communications. 2017;8:15539. DOI: https://doi.org/10.1038/ncomms15539
Masuda T, Low SK, Akiyama M, et al. GWAS of five gynecologic diseases and cross-trait analysis in Japanese. European Journal of Human Genetics. 2020;28:95-107. DOI: https://doi.org/10.1038/s41431-019-0495-1
Cha PC, Takahashi A, Hosono N, et al. A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. Nature Genetics. 2011;43:447-450. DOI: https://doi.org/10.1038/ng.805
Rafnar T, Gunnarsson B, Stefansson OA, et al. Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits. Nature Communications. 2018;9:3636. DOI: https://doi.org/10.1038/s41467-018-05428-6
Välimäki N, Kuisma H, Pasanen A, et al. Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability. eLife. 2018;7:e37110. DOI: https://doi.org/10.7554/eLife.37110
Gallagher CS, Mäkinen N, Harris HR, et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nature Communications. 2019;10:4857. DOI: https://doi.org/10.1038/s41467-019-12536-4
Edwards TL, Giri A, Hellwege JN, et al. A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids. Frontiers in Genetics. 2019;10:511. DOI: https://doi.org/10.3389/fgene.2019.00511
Radzinsky VE, Altuchova OB. Molecular-genetic determinants of infertility in genital endometryosis. Research Results in Biomedicine. 2018;4(3):28-37. Russian. DOI: https://doi.org/10.18413/2313-8955-2018-4-3-0-3
Golovchenko IO. Genetic determinants of sex hormone levels in endometriosis patients. Research Results in Biomedicine. 2023;9(1):5-21. Russian. DOI: https://doi.org/10.18413/2658-6533-2023-9-1-0-1
Ruth KS, Campbell PJ, Chew S, et al. Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes. European Journal of Human Genetics. 2016;24:284-290. DOI: https://doi.org/10.1038/ejhg.2015.102
He C, Kraft P, Chasman DI, Buring JE, et al. A large-scale candidate gene association study of age at menarche and age at natural menopause. Human Genetics. 2010;128:515-527. DOI: https://doi.org/10.1007/s00439-010-0878-4
Stolk L, Perry JRB, Chasman DI, et al. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nature Genetics. 2012;44:260-268. DOI: https://doi.org/10.1038/ng.1051
Gajbhiye R, Fung JN, Montgomery GW. Complex genetics of female fertility. npj Genomic Medicine. 2018;3:29. DOI: https://doi.org/10.1038/s41525-018-0068-1
Rahmioglu N, Macgregor S, Drong AW, et al. Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. Human Molecular Genetics. 2015;24(4):1185-1199. DOI: https://doi.org/10.1093/hmg/ddu516
Fernández-Rhodes L, Demerath EW, Cousminer DL, et al. Association of adiposity genetic variants with menarche timing in 92,105 women of European descent. American Journal of Epidemiology. 2013;178(3):451-460. DOI: https://doi.org/10.1093/aje/kws473
Chen J, Lipska BK, Halim N, et al. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. American Journal of Human Genetics. 2004;75:807-821. DOI: https://doi.org/10.1086/425589
Feng Y, Zha X, Zhou C, et al. The associations between the Val158Met in the catechol-O-methyltransferase (COMT) gene and the risk of uterine leiomyoma (ULM). Gene. 2013;529(2):296-299. DOI: https://doi.org/10.1016/j.gene.2013.07.019
Zhai J, Jiang L, Wen A, et al. Analysis of the relationship between COMT polymorphisms and endometriosis susceptibility. Medicine. 2019;98(1):e13933. DOI: https://doi.org/10.1097/MD.0000000000013933
Day FR, Bulik-Sullivan B, Hinds DA, et al. Shared genetic aetiology of puberty timing between sexes and with health-related outcomes. Nature Communications. 2015;6:8842. DOI: https://doi.org/10.1038/ncomms9842
Day FR, Elks CE, Murray A, et al. Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study. Scientific Reports. 2015;5:11208. DOI: https://doi.org/10.1038/srep11208
Nothnick WB. Non-coding RNAs in Uterine Development, Function and Disease. Advances in experimental medicine and biology. 2016;886:171-189. DOI: https://doi.org/10.1007/978-94-017-7417-8_9

All journals

Send article

Research Results in Biomedicine is included in the scientific database of the RINTs (license agreement No. 765-12/2014 dated 08.12.2014).

The journal is included in the list of peer-reviewed scientific publications recommended by the Higher Attestation Commission

The journal is indexed by the following scientific databases and platforms

Research Results in Biomedicine (ISSN 2658-6533)

The journal materials and website are licensed under Creative Commons «Attribution» 4.0 International.

The Founder: Federal State Autonomous Educational Institution of Higher Education "Belgorod National Research University"The Founder’s address: 85 Pobedy Street, Belgorod, the Belgorod region, 308015, Russia

The Publisher: Federal State Autonomous Educational Institution of HigherEducation "Belgorod National Research University" The Founder’s address:85 Pobedy Street, Belgorod, the Belgorod region, 308015, Russia

Editors Office: chief editor Mikhail I. Churnosov, e-mail: RR_MedPharm@bsu.edu.ru, phone: +7 (4722) 30-14-03.

Regulations on the Journal

Certificate

Have questions?
You can write to us:

✉ Content manager

✉ Site administration

✉ Executive Secretary