Gestational Diabetes Mellitus and Cancer Risk in Pediatrics: A Molecular Pathway and Future Approach

Document Type : review article

Authors

1 Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran.

2 School of medicine, Tabriz University of medical Science, Tabriz,

3 Department of gynecology and obstructive, Mazandaran University of Medical Science, Mazandaran, Iran.

4 Assistant Professor of Internal Medicine Department of Internal Medicine, School of Medicine Hazrat-e Rasool General Hospital Iran University of Medical Sciences.

5 Shahid Akbarabadi Clinical Research Development Unit (SHACRDU), School of Medicine, Iran University of Medical Sciences, Tehran, Iran

6 Department of Obstetrics and Gynecology, Imam Sajad Hospital, Yasuj University of Medical Sciences, Yasuj, Iran

7 Department of Gynecology and Obstetrics, Yasuj University of Medical Sciences, Yasuj, Iran.

Abstract

Gestational Diabetes Mellitus (GDM) is a condition that affects the physiology of the mother and fetus during pregnancy. In addition, it has been shown that it also plays a role in the occurrence and progression of pediatric cancer. Epigenetic changes are one of the risk factors that affect pediatric cancer.  Moreover, hyperinsulinemia and hyperglycemia are among the conditions that can play a role in childhood cancer due to GDM.  In many cases, inflammatory factors activate the NF-κB pathway and lead to inflammation. Furthermore, inhibition of apoptosis inducing factors causes the emergence and proliferation of cancer cells. Also, PI3K/AKT, mTOR, STAT/NF-kB pathways are among the most important pathways involved in the pathogenesis of pediatric cancer. Epigenetic changes, hyperinsulinemia, and hypoglycemia can increase the probability of cancer in children by changing the expression of some genes and signaling pathways. Identifying these pathways can help in the design of treatment strategies and lead to the prevention of cancer and increase the survival of patients.

Keywords

References

  1. Steliarova-Foucher E, Colombet M, Ries LA, Moreno F, Dolya A, Bray F, Hesseling P, Shin HY, Stiller CA; IICC-3 contributors. International incidence of childhood cancer, 2001–10: a population-based registry study. The Lancet Oncology. 2017; 18(6):719-31.
  2. Al-Azemi M, Raghupathy R, Azizieh F. Pro-inflammatory and anti-inflammatory cytokine profiles in fetal growth restriction. Clin Exp Obstet Gynecol. 2017; 44(1):98-103.
  3. Dimasuay KG, Boeuf P, Powell TL, Jansson T. Placental responses to changes in the maternal environment determine fetal growth. Frontiers in physiology. 2016; 7:12.
  4. Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE, Sklar CA, Robison LL, Diller L. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. The lancet oncology. 2013; 14(9):873-81.
  5. Tabatabaei MM. Gestational weight gain, prepregnancy body mass index related to pregnancy outcomes in KAZERUN, FARS, IRAN. Journal of prenatal medicine. 2011; 5(2):35.
  6. Chow EJ, Stratton KL, Leisenring WM, Oeffinger KC, Sklar CA, Donaldson SS, Ginsberg JP, Kenney LB, Levine JM, Robison LL, Shnorhavorian M, Stovall M, Armstrong GT, Green DM. Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. The Lancet Oncology. 2016; 17(5):567-76.
  7. Yan P, Wang Y, Yu X, Liu Y, Zhang Z-J. Maternal diabetes and risk of childhood malignancies in the offspring: a systematic review and meta-analysis of observational studies. Acta Diabetologica. 2021; 58:153-68.
  8. Holly JM, Biernacka K, Perks CM. The neglected insulin: IGF-II, a metabolic regulator with implications for diabetes, obesity, and cancer. Cells. 2019; 8(10):1207.
  9. Galliano D, Bellver J. Female obesity: short-and long-term consequences on the offspring. Gynecological Endocrinology. 2013; 29(7):626-31.
  10. Nouri B, Sarani S, Arab M, Bakhtiari M, Sarbazi F, Karimi A. Comparative study of laparoscopic versus laparotomic surgery for adnexal masses. Journal of Obstetrics, Gynecology and Cancer Research. 2022; 7(3):230-4.
  11. Samidurai A, Roh SK, Prakash M, Durrant D, Salloum FN, Kukreja RC, Das A. STAT3-miR-17/20 signalling axis plays a critical role in attenuating myocardial infarction following rapamycin treatment in diabetic mice. Cardiovascular research. 2020; 116(13):2103-15.
  12. Bridgeman SC, Ellison GC, Melton PE, Newsholme P, Mamotte CDS. Epigenetic effects of metformin: from molecular mechanisms to clinical implications. Diabetes, Obesity and Metabolism. 2018; 20(7):1553-62.
  13. Huang Z-q, Liao Y-q, Huang R-z, Chen J-p, Sun H-l. Possible role of TCF7L2 in the pathogenesis of type 2 diabetes mellitus. Biotechnology & Biotechnological Equipment. 2018; 32(4):830-4.
  14. Kang J, Lee C-N, Li H-Y, Hsu K-H, Lin S-Y. Genome-wide DNA methylation variation in maternal and cord blood of gestational diabetes population. Diabetes research and clinical practice. 2017; 132:127-36.
  15. Karsy M, Arslan E, Moy F. Current progress on understanding microRNAs in glioblastoma multiforme. Genes & cancer. 2012; 3(1):3-15.
  16. Jiao Y, Feng Y, Wang X. Regulation of tumor suppressor gene CDKN2A and encoded p16-INK4a protein by covalent modifications. Biochemistry (Moscow). 2018; 83:1289-98.
  17. Franzago M, Fraticelli F, Stuppia L, Vitacolonna E. Nutrigenetics, epigenetics and gestational diabetes: consequences in mother and child. Epigenetics. 2019; 14(3):215-35.
  18. Liu L, Xu H, Zhao H, Jiang C. STEAP4 Inhibits HIF-1α/PKM2 signaling and reduces high glucose-induced apoptosis of retinal vascular endothelial cells. Diabetes, Metabolic Syndrome and Obesity. 2020:2573-82.
  19. Bilen A, Calik I, Yayla M, Dincer B, Tavaci T, Cinar I, Bilen H, Cadirci E, Halici Z, Mercantepe F. Does daily fasting shielding kidney on hyperglycemia-related inflammatory cytokine via TNF-α, NLRP3, TGF-β1 and VCAM-1 mRNA expression. International journal of biological macromolecules. 2021; 190:911-8.
  20. Ji L, Shi X, Wang G, Wu H, Hu Z. Overexpressing six-transmembrane protein of prostate 2 (STAMP2) alleviates sepsis-induced acute lung injury probably by hindering M1 macrophage polarization via the NF-κB pathway. Folia Histochemica et Cytobiologica. 2023; 61(1):34-46.
  21. Zhang Q, Wu S, Sun G, Zhang R, Li X, Zhang Y, Huang F. Hyperglycemia aggravates monocyte-endothelial adhesion in human umbilical vein endothelial cells from women with gestational diabetes mellitus by inducing Cx43 overexpression. Annals of Translational Medicine. 2021; 9(3).
  22. Turhan A, Pereira MT, Schuler G, Bleul U, Kowalewski MP. Hypoxia-inducible factor (HIF1alpha) inhibition modulates cumulus cell function and affects bovine oocyte maturation in vitro. Biology of reproduction. 2021; 104(2):479-91.
  23. Talakatta G, Sarikhani M, Muhamed J, Dhanya K, Somashekar BS, Mahesh PA, Anand Mahesh P, Sundaresan N, Ravindra PV. Diabetes induces fibrotic changes in the lung through the activation of TGF-β signaling pathways. Scientific reports. 2018; 8(1):11920.
  24. Wei J, Zhang Y, Luo Y, Wang Z, Bi S, Song D, Dai Y, Wang T, Qiu L, Wen L, Yuan L, Yang JY. Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1–Nrf2, Tgfβ1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice. Free Radical Biology and Medicine. 2014; 67:91-102.
  25. Endo F, Komine O, Fujimori-Tonou N, Katsuno M, Jin S, Watanabe S, Sobue G, Dezawa M, Wyss-Coray T, Yamanaka K. Astrocyte-derived TGF-β1 accelerates disease progression in ALS mice by interfering with the neuroprotective functions of microglia and T cells. Cell reports. 2015; 11(4):592-604.
  26. Naing A, LoRusso P, Fu S, Hong DS, Anderson P, Benjamin RS, Ludwig J, Chen HX, Doyle LA, Kurzrock R. Insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family tumors. Clinical Cancer Research. 2012; 18(9):2625-31.
  27. Yang W, Wang J, Chen Z, Chen J, Meng Y, Chen L, Chang Y, Geng B, Sun L, Dou L, Li J, Guan Y, Cui Q, Yang J. NFE2 induces miR-423-5p to promote gluconeogenesis and hyperglycemia by repressing the hepatic FAM3A-ATP-Akt pathway. Diabetes. 2017; 66(7):1819-32.
  28. Lv N, Gao Y, Guan H, Wu D, Ding S, Teng W, Shan Z. Inflammatory mediators, tumor necrosis factor-α and interferon-γ, induce EMT in human PTC cell lines. Oncology letters. 2015; 10(4):2591-7.
  29. Nishida H, Sohara E, Nomura N, Chiga M, Alessi DR, Rai T, Sasaki S, Uchida S. PI3K/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice. Hypertension. 2012; 60(4):981.
  30. Lai HL, Kartal J, Mitsnefes M. Hyperinsulinemia in pediatric patients with chronic kidney disease: the role of tumor necrosis factor-α. Pediatric Nephrology. 2007; 22:1751-6.
  31. Zhang AM, Magrill J, de Winter TJ, Hu X, Skovsø S, Schaeffer DF, Kopp JL, Johnson JD. Endogenous hyperinsulinemia contributes to pancreatic cancer development. Cell metabolism. 2019; 30(3):403-4.
  32. Lv Q-Y, Xie B-Y, Yang B-Y, Ning C-C, Shan W-W, Gu C, Luo XZ, Chen XJ, Zhang ZB, Feng YJ. Increased TET1 expression in inflammatory microenvironment of hyperinsulinemia enhances the response of endometrial cancer to estrogen by epigenetic modulation of GPER. Journal of Cancer. 2017; 8(5):894.
  33. Zhu G, Huang Y, Wu C, Wei D, Shi Y. Activation of G-protein-coupled estrogen receptor inhibits the migration of human non-small cell lung cancer cells via IKK-β/NF-κB signals. DNA and Cell Biology. 2016; 35(8):434-42.
  34. De Francesco EM, Sims AH, Maggiolini M, Sotgia F, Lisanti MP, Clarke RB. GPER mediates the angiocrine actions induced by IGF1 through the HIF-1α/VEGF pathway in the breast tumor microenvironment. Breast Cancer Research. 2017; 19:1-14.
  35. Liu S, Zhang Q, Chen C, Ge D, Qu Y, Chen R, Fan YM, Li N, Tang WW, Zhang W, Zhang K, Wang AR, Rowan BG, Hill SM, Sartor O, Abdel-Mageed AB, Myers L, Lin Q, You Z. Hyperinsulinemia enhances interleukin-17-induced inflammation to promote prostate cancer development in obese mice through inhibiting glycogen synthase kinase 3-mediated phosphorylation and degradation of interleukin-17 receptor. Oncotarget. 2016; 7(12):13651.
  36. Brunsing RL, Owens KS, Prossnitz ER. The G protein-coupled estrogen receptor (GPER) agonist G-1 expands the regulatory T cell population under T (H) 17 polarizing conditions. Journal of immunotherapy (Hagerstown, Md: 1997). 2013; 36(3):190.
  37. Chen X-W, Zhou S-F. Inflammation, cytokines, the IL-17/IL-6/STAT3/NF-κB axis, and tumorigenesis. Taylor & Francis; 2015. p. 2941-6.
  38. Cortez D. Feldman MD, Mummidi S, Valente AJ, Steffensen B, Vincenti M, Barnes JL, Chandrasekar B. IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK-and ERK1/2-dependent C/EBP-beta, NF-kappaB, and AP-1 activation Am J Physiol Heart Circ Physiol. 2007;293:H3356-H65.
  39. Liu R, Guan S, Gao Z, Wang J, Xu J, Hao Z, Hao Z, Zhang Y, Yang S, Guo Z, Yang J, Shao H, Chang B. Pathological hyperinsulinemia and hyperglycemia in the impaired glucose tolerance stage mediate endothelial dysfunction through miR-21, PTEN/AKT/eNOS, and MARK/ET-1 pathways. Frontiers in Endocrinology. 2021; 12:644159.
  40. Bingisser RM, Tilbrook PA, Holt PG, Kees UR. Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. The Journal of Immunology. 1998; 160(12):5729-34.
  41. Han M, Liu M, Wang Y, Chen X, Xu J, Sun Y, Zhao L, Qu H, Fan Y, Wu C. Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN. PloS one. 2012; 7(6):e39520.
Journal of Pediatric Perspectives
Volume 11, Issue 8
August 2023
Pages 18172-18179

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