Endometrial hyperplasia in women with comorbid obesity working in contact with organic solvents
- Authors: Marinkin I.O.1, Shpagina L.A.1, Lisova E.S.1, Kotova O.S.1, Kuznetsova G.V.1, Loktin E.M.1, Karmanovskaya S.A.1
-
Affiliations:
- Novosibirsk State Medical University, Ministry of Health of the Russian Federation
- Issue: No 3 (2023)
- Pages: 57-64
- Section: Original Articles
- URL: https://journals.rcsi.science/0300-9092/article/view/258612
- DOI: https://doi.org/10.18565/aig.2022.289
- ID: 258612
Cite item
Abstract
Objective: To determine the effect of organic solvents on the clinical, morphological, and molecular characteristics of endometrial hyperplasia in relation to obesity.
Materials and methods: This single-center cross-sectional study included 140 women with histologically confirmed endometrial hyperplasia and occupational exposure to organic solvents; of these, 70 women were obese. The comparison group comprised140 women with endometrial hyperplasia without occupational health risks; of these, 68 were obese. The participants were 57 (45; 64) and 56 (46; 63) years of age and had been menopausal for more than 2 years. The concentrations of organic solvents exceeded the maximum permissible exposure limit by a factor of 1.1 to 5, and the duration of exposure was 22 (18; 28) years. All patients underwent pelvic ultrasound, hysteroscopy with biopsy, and histological and immunohistochemical (Ki-67, estrogen, and progesterone receptor) examinations. Protein concentrations in the blood were determined using a solid-phase enzyme immunoassay.
Results: Organic solvent exposure was associated with a higher incidence of atypical endometrial hyperplasia, mainly in the obese subgroup – 24/70 (34.3%). In the non-obese subgroup, it was 13/70 (18.6%) in the comparison group (7/68 (10.3%) vs. 5/72 (6.9%), p=0.003). There was simultaneous increase in Ki-67 expression (for atypical endometrial hyperplasia 55.7% (53.5; 60,1)% и 42,0 (40,4; 45.6)% in obese and non-obese subgroups), increased frequency of abnormal uterine bleeding – 20/70 (28.5%) and 11/70(15.7%), M-echo thickness – 12 (11; 13) and 9.0 (9; 9.5) mm), blood concentrations of interleukins 1β and 6 (higher in obesity), transforming growth factor β1, platelet-derived growth factor-AB, fibroblast growth factor-2 (independent of obesity), p<0.01. The organic solvent exposure group showed correlations between atypical endometrial hyperplasia and age, maximum single concentrations of toluene, waist circumference, Ki-67, and platelet-derived growth factor-AB.
Conclusion: This study identified the clinical and pathogenetic features of endometrial hyperplasia in women exposed to organic solvents associated with comorbid obesity.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
Igor O. Marinkin
Novosibirsk State Medical University, Ministry of Health of the Russian Federation
Author for correspondence.
Email: rector@ngmu.ru
ORCID iD: 0000-0002-9409-4823
Dr. Med. Sci., Professor, Merited Doctor of the Russian Federation, Rector, Head of the Department of Obstetrics and Gynecology
Russian Federation, NovosibirskLyubov A. Shpagina
Novosibirsk State Medical University, Ministry of Health of the Russian Federation
Email: lashpagina@gmail.com
ORCID iD: 0000-0003-0871-7551
Dr. Med. Sci., Professor, Merited Doctor of the Russian Federation, Head of the Internal Medicine and Rehabilitation Department
Russian Federation, NovosibirskEvgeniya S. Lisova
Novosibirsk State Medical University, Ministry of Health of the Russian Federation
Email: mkb-2@yandex.ru
ORCID iD: 0000-0002-3469-8756
PhD Student at the Internal Medicine and Rehabilitation Department
Russian Federation, NovosibirskOlga S. Kotova
Novosibirsk State Medical University, Ministry of Health of the Russian Federation
Email: ok526@yandex.ru
ORCID iD: 0000-0003-0724-1539
Dr. Med. Sci., Associate Professor at the Internal Medicine and Rehabilitation Department
Russian Federation, NovosibirskGalina V. Kuznetsova
Novosibirsk State Medical University, Ministry of Health of the Russian Federation
Email: mkb-2@yandex.ru
ORCID iD: 0000-0001-7428-9159
PhD, Associate Professor at the Internal Medicine and Rehabilitation Department
Russian Federation, NovosibirskEvgenij M. Loktin
Novosibirsk State Medical University, Ministry of Health of the Russian Federation
Email: mkb-2@yandex.ru
ORCID iD: 0000-0002-7370-6958
Dr. Med. Sci., Associate Professor at the Internal Medicine and Rehabilitation Department
Russian Federation, NovosibirskSvetlana A. Karmanovskaya
Novosibirsk State Medical University, Ministry of Health of the Russian Federation
Email: mkb-2@yandex.ru
ORCID iD: 0000-0003-3446-8018
Dr. Med. Sci., Associate Professor at the Internal Medicine and Rehabilitation Department
Russian Federation, NovosibirskReferences
- Green M.P., Harvey A.J., Finger B.J., Tarulli G.A. Endocrine disrupting chemicals: Impacts on human fertility and fecundity during the peri-conception period. Environ. Res. 2021; 194: 110694. https://dx.doi.org/10.1016/ j.envres.2020.110694
- Spinder N., Prins J.R., Bergman J.E.H., Smidt N., Kromhout H., Boezen H.M. et al. Congenital anomalies in the offspring of occupationally exposed mothers: a systematic review and meta-analysis of studies using expert assessment for occupational exposures. Hum. Reprod. 2019; 34(5): 903-19. https://dx.doi.org/10.1093/humrep/dez033
- Yu Q., Zhang L., Hou K., Li J., Liu S., Huang K. et al. Relationship between air pollutant exposure and gynecologic cancer risk. Int. J. Environ. Res. Public Health. 2021; 18(10): 5353. https://dx.doi.org/10.3390/ijerph18105353
- Karami S., Bassig B., Stewart P.A., Lee K.M.., Rothman N., Moore L.E. et al. Occupational trichloroethylene exposure and risk of lymphatic and haematopoietic cancers: a meta-analysis. Occup. Environ. Med. 2013; 70(8): 591-9. https://dx.doi.org/10.1136/oemed-2012-101212
- Onyije F.M., Hosseini B., Togawa K., Schüz J., Olsson A. Cancer incidence and mortality among petroleum industry workers and residents living in oil producing communities: a systematic review and meta-analysis. Int. J. Environ. Res. Public Health. 2021; 18: 4343. https://dx.doi.org/10.3390/ijerph18084343
- International Agency for the Research on Cancer. List of classifications. Available at: https://monographs.iarc.who.int/list-of-classifications
- Подзолкова Н.М., Коренная В.В. Современные представления об этиологии, патогенезе и принципах лечения гиперплазии эндометрия. Акушерство и гинекология. 2021; 8: 192-9. [Podzolkova N.M., Korennaya V.V. Modern ideas about the etiology, pathogenesis and principles of treatment of endometrial hyperplasia. Obstetrics and Gynecology. 2021; (8): 192-9. (in Russian)]. https://dx.doi.org/10.18565/aig.2021.8.192-199
- Клинышкова Т.В., Турчанинов Д.В., Фролова Н.Б. Клинико-эпидемиологические аспекты рака тела матки с позиции профилактики рецидивирования гиперплазии эндометрия. Акушерство и гинекология. 2020; 1: 135-40. [Klinyshkova T.V., Turchaninov D.V., Frolova N.B. Clinical and epidemiological aspects of corpus uteri cancer in the context of prevention of recurrent endometrial hyperplasia. Obstetrics and Gynecology. 2020; (1): 135-140. (in Russian)]. https://dx.doi.org/10.18565/ aig.2020.1.135-140
- Salman M.C., Usubutun A., Boynukalin K., Yuce K. Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia. J. Gynecol. Oncol. 2010; 21(2): 97-101. https://dx.doi.org/10.3802/jgo.2010.21.2.97
- Vilos G.A., Oraif A., Vilos A.G., Ettler H., Edris F., Abu-Rafea B. Long-term clinical outcomes following resectoscopic endometrial ablation of non-atypical endometrial hyperplasia in women with abnormal uterine bleeding. J. Minim. Invasive Gynecol. 2015; 22(1): 66-77. https://dx.doi.org/10.1016/ j.jmig.2014.07.009
- Измеров Н.Ф., ред. Профессиональная патология. Национальное руководство. М.: ГЭОТАР-Медиа; 2011. 784с. [Izmerov N.F., ed. Occupational medicine. National guidelines. Мoscow: GEOTAR-Media; 2011. 784p. (in Russian)].
- Адамян Л.В., Андреева Е.Н., Артымук Н.В., Башмакова Н.В., Беженарь В.Ф., Белокриницкая Т.Е. и др. Гиперплазия эндометрия. Федеральные клинические рекомендации. Доступно по: https://cr.minzdrav.gov.ru/schema/646_1 [Adamyan L.V., Andreeva E.N., Artymuk N.V., Bashmakova N.V., Bezhenar V.F., Belokrinickaya T.E. et al. Endometrial hyperplasia. Federal clinical guidelines. Available at: https://cr.minzdrav.gov.ru/schema/ 646_1 (in Russian)].
- Raffone A., Travaglino A., Saccone G., Insabato L., Mollo A., De Placido G., Zullo F. Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis. Arch. Gynecol. Obstet. 2019; 299(5): 1233-42. https://dx.doi.org/10.1007/ s00404-019-05103-1
- Alberti K.G.M.M., Zimmet P., Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet. Med. 2006; 23(5): 469-80. https://dx.doi.org/10.1111/j.1464-5491.2006.01858.x
- Bojanic D., Ljubojevic M., Krivokapic D., Gontarev S. Waist circumference, waist-to-hip ratio, and waist-to-height ratio reference percentiles for abdominal obesity among Macedonian adolescents. Nutr. Hosp. 2020; 37(4): 786-93. https://dx.doi.org/10.20960/nh.03006
- Liang Q., Ma D., Gao R.F., Yu K.D. Effect of Ki-67 Expression levels and histological grade on breast cancer early relapse in patients with different immunohistochemical-based subtypes. Sci. Rep. 2020; 10(1): 7648. https://dx.doi.org/10.1038/s41598-020-64523-1
- Hetemaki N., Savolainen-Peltonen H., Tikkanen M.J., Wang F., Paatela H., Hamalainen E. et al. Estrogen metabolism in abdominal subcutaneous and visceral adipose tissue in postmenopausal women. J. Clin. Endocrinol. Metab. 2017; 102(12): 4588-95. https://dx.doi.org/10.1210/jc.2017-01474
- Caja L., Dituri F., Mancarella S., Caballero-Diaz D., Moustakas A., Giannelli G., Fabregat I. TGF-β and the tissue microenvironment: relevance in fibrosis and cancer. Int. J. Mol. Sci. 2018; 19(5): 1294. https://dx.doi.org/10.3390/ijms19051294
- Chung J.Y., Chan M.K., Li J.S., Chan A.S., Tang P.C., Leung K.T. et al. TGF-β signaling: from tissue fibrosis to tumor microenvironment. Int. J. Mol. Sci. 2021; 22(14): 7575. https://dx.doi.org/10.3390/ijms22147575
- Bent R., Moll L., Grabbe S., Bros M. Interleukin-1 Beta-A friend or foe in malignancies? Int. J. Mol. Sci. 2018; 19(8): 2155. https://dx.doi.org/10.3390/ijms19082155
- Mantovani A., Dinarello C.A., Molgora M., Garlanda C. Interleukin-1 and related cytokines in the regulation of inflammation and immunity. Immunity. 2019; 50(4): 778-95. https://dx.doi.org/10.1016/j.immuni.2019.03.012
- Unver N., McAllister F. IL-6 family cytokines: key inflammatory mediators as biomarkers and potential therapeutic targets. Cytokine Growth Factor Rev. 2018; 41: 10-7. https://dx.doi.org/10.1016/j.cytogfr.2018.04.004
- Hillege M.M.G., Galli Caro R.A., Offringa C., de Wit G.M.J., Jaspers R.T., Hoogaars W.M.H. TGF-β regulates collagen type i expression in myoblasts and myotubes via transient Ctgf and Fgf-2 expression. Cells. 2020; 9(2): 375. https://dx.doi.org/10.3390/cells9020375
- Paolini C., Agarbati S., Benfaremo D., Mozzicafreddo M., Svegliati S., Moroncini G. PDGF/PDGFR: a possible molecular target in scleroderma fibrosis. Int. J. Mol. Sci. 2022; 23(7): 3904. https://dx.doi.org/10.3390/ ijms23073904