The impact of obesity on the development of certain cancers in patients with type 2 diabetes

T.S.  Vatseba; L.K.  Sokolova; M.D.  Tronko; I.K.  Churpiy; M.O.  Vatseba; V.V.  Derpak

doi:10.26641/2307-0404.2021.2.234627

Authors

T.S. Vatseba Ivano-Frankivsk National Medical University, Halytska str., 2, Ivano-Frankivsk, 76018, Ukraine, Ukraine https://orcid.org/0000-0001-7849-2242
L.K. Sokolova SI «V.P. Komisarenko Institute of Endocrinology and Metabolism, NAMN of Ukraine», Vyshhorodska, 69, Kyiv, 04114, Ukraine, Ukraine https://orcid.org/0000-0003-0011-0106
M.D. Tronko SI «V.P. Komisarenko Institute of Endocrinology and Metabolism, NAMN of Ukraine», Vyshhorodska, 69, Kyiv, 04114, Ukraine, Ukraine https://orcid.org/0000-0001-7421-0981
I.K. Churpiy Ivano-Frankivsk National Medical University, Halytska str., 2, Ivano-Frankivsk, 76018, Ukraine, Ukraine https://orcid.org/0000-0003-1735-9418
M.O. Vatseba Ivano-Frankivsk National Medical University, Halytska str., 2, Ivano-Frankivsk, 76018, Ukraine, Ukraine https://orcid.org/0000-0001-7070-1740
V.V. Derpak Ivano-Frankivsk National Medical University, Halytska str., 2, Ivano-Frankivsk, 76018, Ukraine, Ukraine https://orcid.org/0000-0002-5025-7184

DOI:

https://doi.org/10.26641/2307-0404.2021.2.234627

Keywords:

obesity, diabetes mellitus, cancer risk

Abstract

The aim of the study was to investigate the effect of obesity on the development of cancer of certain localizations in patients with type 2 diabetes mellitus (T2D) and to explain the association mechanisms of obesity in diabetes and cancer. The study included retrospective analysis of first time diagnosed cancer cases in patients with T2D in 2012-2016 in Ivano-Frankivsk region. Analysis of the data was carried out using Statistica 12.0 (StatSoft Inc., USA) program. The data are presented in the tables as M ± SD (M ± standard deviation). Differences between the studied parameters were determined using the ANOVA- test, taking into account the Bonferroni correction. The relationship between the studied data was evaluated using the criterion of chi-square with Yates correction (χ²). The odds ratio (OR), 95% confidence interval, the positive and negative predictive value were calculated to determine the association between two events. The differences were considered significant at p < 0.05. According to the results, 533 cases of the first time diagnosed cancer were detected in patients with T2D. It was found that obesity is inherent in women with breast, uterine, ovarian and colorectal cancer; for men with prostate cancer and with colorectal cancer. According to the criterion of χ², the effect of obesity on the incidence of breast cancer in women (x²=8.46; p<0.05), and prostate cancer (x²=7.02; p<0.05) and colorectal cancer (x²=7.94; p<0.05) in men was proven. OR revealed an increased risk of breast cancer in women [OR=2.06; 95% CI (1.28-3.29); p<0.05], and prostate cancer [OR=2.94; 95% CI (1.37-6.32); p<0.05] and colorectal cancer [OR=2.87; 95% CI (1.42-5.82); p<0.05] in men associated with obesity. Thus, among patients with T2D, obesity increases the risk of breast cancer in women, prostate cancer and colorectal cancer in men. The mechanisms of association of obesity and cancer in patients with T2D are hyperglycemia, hyperinsulinemia, cytokine imbalance, hyperestrogenism (in estrogen-dependent cancer), and intestinal dysbiosis (in colorectal cancer).

References

Antonomonov MYu. [Mathematical processing and analysis of biomedical data]. Kyiv; 2017;578. Russian.

Vatseba TS, Sokolova LK. [Pathogenetic mechanisms of oncogenesis on the background of diabetes mellitus and analysis of oncological morbidity of patients with diabetes mellitus in the Carpathian region]. Endocrinology. 2018;2(23):128-37. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/enkrl_2018_23_2_6.

Lekhan VM, Voronenko YuV, Maksymenko OP, Zyukov OL, Hubar IO. [Epidemiological methods for studying non-infectious diseases]. Dnipropetrovsk; 2004;184. Ukrainian.

Lavalette C, Trétarre B, Rebillard X, et al. Abdominal obesity and prostate cancer risk: epidemiological evidence from the EPICAP study. Oncotarget. 2018;9(77):34485-94. doi: https://doi.org/10.18632/oncotarget.26128

Marín-Aguilar F, Pavillard LE, Giampieri F, et al. Adenosine Monophosphate (AMP)-Activated Protein Kinase: A New Target for Nutraceutical Compounds. Int J Mol Sci. 2017;18(2):288. doi: https://doi.org/10.3390/ijms18020288

Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):359-86. doi: https://doi.org/10.1002/ijc.29210

Eroğlu O, Yuksel S. Statistical Method Selection İn Medical Research. Experimental biology. 2019;29:364-71. doi: https://doi.org/10.26449/sssj.1219

International Diabetes Federation. IDF Diabetes Atlas. 9th ed. Brussels; 2019. p. 176.

Oberaigner W, Ebenbichler C, Oberaigner K, et al. Increased cancer incidence risk in type 2 diabetes mellitus: results from a cohort study in Tyrol/Austria. BMC Public Health. 2014;14:1058. doi: https://doi.org/10.1186/1471-2458-14-1058

McNabney SM, Henagan TM. Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance. Nutrients. 2017;9(12):1348. doi: https://doi.org/10.3390/nu9121348

Cirillo F, Catellani C, Sartori C, et al. Obesity, Insulin Resistance, and Colorectal Cancer: Could miRNA Dys¬regu¬lation Play A Role? Int J Mol Sci. 2019;20(12):2922. doi: https://doi.org/10.3390/ijms20122922

Pilleron S, Sarfati D, Janssen-Heijnen M, et al. Global cancer incidence in older adults, 2012 and 2035: A population-based study. Int J Cancer. 2019;144(1):49-58. doi: https://doi.org/10.1002/ijc.31664

Poloz Y, Stambolic V. Obesity and cancer, a case for insulin signaling. Cell Death Dis. 2015;6(12):e2037. doi: https://doi.org/10.1038/cddis.2015.381

STATISTICA (data analysis software system), version 12. StatSoft, Inc. USA: Tulsa; 2014. Available from: https://www.statsoft.com

Rajagopala SV, Vashee S, Oldfield LM, et al. The Human Microbiome and Cancer. Cancer Prev Res. 2017;10(4):226-34.

doi: https://doi.org/10.1158/1940-6207.CAPR-16-0249

Ukrainian cancer registry statistics, 2017. "Cancer in Ukraine", 2017-2018, Bulletin of national cancer registry of Ukraine. 2017;20.

Available from: http://www.ncru.inf.ua

Vatseba TS. Influence of pathogenetic factors of type 2 diabetes on activation of PI3K/AkT/mTOR pathway and on the development of endometrial and breast cancer. Regulatory Mechanisms in Biosystems. 2019;10(3):295-99. doi: https://doi.org/10.15421/021945

Vatseba TS, Sokolova LK, Pushkarev VV, et al. Activation of the PI3K/Akt/mTOR/p70S6K1 signaling cascade in the mononuclear cells of peripheral blood: association with insulin and insulin-like growth factor levels in the blood of patients with cancer and diabetes. Cytology and Genetics. 2019;53:489-493. doi: https://doi.org/10.3103/S0095452719060112

Wu Y, Liu Y, Dong Y, Vadgama J. Diabetes-associated dysregulated cytokines and cancer. Integr Cancer Sci Ther. 2016;3(1):370-8. doi: https://doi.org/10.15761/ICST.1000173

Yang X, Wang J. The Role of Metabolic Syndrome in Endometrial Cancer: A Review. Front Oncol. 2019;9:744, doi: https://doi.org/10.3389/fonc.2019.00744

Yasuda MT, Sakakibara H, Shimoi K. Estrogen and stress-induced DNA damage in breast cancer and chemo¬pre¬vention with dietary flavonoid. Genes Environ. 2017;39:10. doi: https://doi.org/10.1186/s41021-016-0071-7

Zimmet PZ. Diabetes and its drivers: the largest epidemic in human history? Clin Diabetes Endocrinol. 2017;3(1). doi: https://doi.org/10.1186/s40842-016-0039-3

Zinger A, Cho WC, Ben-Yehuda A. Cancer and Aging – the Inflammatory Connection. Aging Dis. 2017;8(5):611-27. doi: https://doi.org/10.14336/AD.2016.1230