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Acromegaly and Cancer

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Acromegaly

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

Malignancy has now exceeded cardiovascular disease as the most common cause of death in acromegaly. This change is an effect of the improving life expectancy in acromegaly due to better disease management with current treatment modalities. In controlled acromegaly, the overall mortality rate from malignancy is the same as the general population, and the trend in cancer deaths is a result of normal aging. However, in those with uncontrolled acromegaly, both overall mortality and cancer-related mortality are increased, and specifically, colon cancer mortality is higher. There has been an ongoing debate for more than 50 years, if there is an increased incidence of cancer in acromegaly. Some studies show a greater risk while others have no added risk. The most recent, large population studies have observed an overall elevated risk of cancer in acromegaly, and the most common cancer types reported are colon and thyroid. New data indicates a greater risk of prostate cancer as well. In addition, colon polyps and thyroid nodules are more numerous in patients with acromegaly. Therefore, current guidelines recommend a colonoscopy at diagnosis and a thorough thyroid exam including a thyroid ultrasound in those patients with palpable nodules. Fine-needle aspiration of thyroid nodules and screening tests for other cancers are based on standard guidelines for the general population. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are not thought to be mutagenic per se, but elevated levels create a permissive environment in which malignant transformation can occur. Tumors can secrete GH and IGF-1 leading to autocrine/paracrine actions, may amplify IGF-1 receptor (IGF1R) expression, and can adopt the GH/IGF-1 signaling pathways, all of which enhance growth and metastasis of malignant cells. Elevated circulating GH and IGF-1 levels in uncontrolled acromegaly may augment the autocrine/paracrine actions of tumor produced hormones. Uncontrolled diabetes resulting from the insulin resistance of acromegaly may further increase the risk of cancer. Recognizing the significant role that the GH/IGF-1 axis plays in malignancy, it is essential to maintain excellent control of acromegaly as well as to emphasize cancer prevention and utilize appropriate screening tests to mitigate cancer risk.

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References

  1. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004;25(1):102–52. https://doi.org/10.1210/er.2002-0022.

    Article  PubMed  CAS  Google Scholar 

  2. Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-1 on mortality in acromegaly. Eur J Endocrinol. 2008;159(2):89–95. https://doi.org/10.1530/EJE-08-0267.

    Article  PubMed  CAS  Google Scholar 

  3. Bolfi F, Neves AF, Boguszewski CL, Nunes-Nogueira VS. Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis. Eur J Endocrinol. 2018;179(1):59–71. https://doi.org/10.1530/EJE-18-0255.

    Article  PubMed  CAS  Google Scholar 

  4. Gadelha MR, Kasuki L, Lim DST, Fleseriu M. Systemic complications of acromegaly and the impact of the current treatment landscape: an update. Endocr Rev. 2019;40(1):268–332. https://doi.org/10.1210/er.2018-00115.

    Article  PubMed  Google Scholar 

  5. Arosio M, Reimondo G, Malchiodi E, et al. Predictors of morbidity and mortality in acromegaly: an Italian survey. Eur J Endocrinol. 2012;167(2):189–98. https://doi.org/10.1530/EJE-12-0084.

    Article  PubMed  CAS  Google Scholar 

  6. Bogazzi F, Colao A, Rossi G, et al. Comparison of the effects of primary somatostatin analogue therapy and pituitary adenomectomy on survival in patients with acromegaly: a retrospective cohort study. Eur J Endocrinol. 2013;169(3):367–76. https://doi.org/10.1530/EJE-13-0166.

    Article  PubMed  CAS  Google Scholar 

  7. Mercado M, Gonzalez B, Vargas G, et al. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J Clin Endocrinol Metab. 2014;99(12):4438–46. https://doi.org/10.1210/jc.2014-2670.

    Article  PubMed  CAS  Google Scholar 

  8. Maione L, Brue T, Beckers A, et al. Changes in the management and comorbidities of acromegaly over three decades: the French acromegaly registry. Eur J Endocrinol. 2017;176(5):645–55. https://doi.org/10.1530/EJE-16-1064.

    Article  PubMed  CAS  Google Scholar 

  9. Esposito D, Ragnarsson O, Granfeldt D, Marlow T, Johannsson G, Olsson DS. Decreasing mortality and changes in treatment patterns in patients with acromegaly from a nationwide study. Eur J Endocrinol. 2018;178(5):459–69. https://doi.org/10.1530/EJE-18-0015. Errata: https://doi.org/10.1530/EJE-18-0015e.

    Article  PubMed  CAS  Google Scholar 

  10. Sherlock M, Ayuk J, Tomlinson JW, et al. Mortality in patients with pituitary disease. Endocr Rev. 2010;31(3):301–42. https://doi.org/10.1210/er.2009-0033.

    Article  PubMed  Google Scholar 

  11. Ritvonen E, Löyttyniemi E, Jaatinen P, Ebeling T, Moilanen L, Nuutila P, Kauppinen-Mäkelin R, Schalin-Jäntti C. Mortality in acromegaly: a 20-year follow-up study. Endocr Relat Cancer. 2016;23(6):469–80. https://doi.org/10.1530/ERC-16-0106.

    Article  PubMed  CAS  Google Scholar 

  12. Ayuk J, Clayton RN, Holder G, Sheppard MC, Stewart PM, Bates AS. Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab. 2004;89(4):1613–7. https://doi.org/10.1210/jc.2003-031584.

    Article  PubMed  CAS  Google Scholar 

  13. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab. 2004;89(2):667–74. https://doi.org/10.1210/jc.2003-031199.

    Article  PubMed  CAS  Google Scholar 

  14. Orme SM, McNally RJ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab. 1998;83(8):2730–4. https://doi.org/10.1210/jcem.83.8.5007.

    Article  PubMed  CAS  Google Scholar 

  15. Kauppinen-Mäkelin R, Sane T, Välimäki MJ, Markkanen H, Niskanen L, Ebeling T, Jaatinen P, Juonala M, Finnish Acromegaly Study Group, Pukkala E. Increased cancer incidence in acromegaly--a nationwide survey. Clin Endocrinol. 2010;72(2):278–9. https://doi.org/10.1111/j.1365-2265.2009.03619.x.

    Article  Google Scholar 

  16. Green J, Cairns BJ, Casabonne D, et al. Height and cancer incidence in the Million Women Study: prospective cohort, and meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol. 2011;12(8):785–94. https://doi.org/10.1016/S1470-2045(11)70154-1.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Liang S, Lv G, Chen W, Jiang J, Wang J. Height and kidney cancer risk: a meta-analysis of prospective studies. J Cancer Res Clin Oncol. 2015;141(10):1799–807. https://doi.org/10.1007/s00432-014-1870-5.

    Article  PubMed  CAS  Google Scholar 

  18. Schouten LJ, Rivera C, Hunter DJ, et al. Height, body mass index, and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomark Prev. 2008;17(4):902–12. https://doi.org/10.1158/1055-9965.EPI-07-2524.

    Article  Google Scholar 

  19. Song X, Gong X, Zhang T, Jiang W. Height and risk of colorectal cancer: a meta-analysis. Eur J Cancer Prev. 2018;27(6):521–9. https://doi.org/10.1097/CEJ.0000000000000390.

    Article  PubMed  Google Scholar 

  20. Aarestrup J, Bjerregaard LG, Meyle KD, et al. Birthweight, childhood overweight, height and growth and adult cancer risks: a review of studies using the Copenhagen School Health Records Register. Int J Obes. 2020;44(7):1546–60. https://doi.org/10.1038/s41366-020-0523-9.

    Article  Google Scholar 

  21. Parra-Soto S, Ho FK, Pell JP, Celis-Morales C. Does insulin-like growth factor moderate the association between height and risk of cancer at 24 sites? Br J Cancer. 2020;123(11):1697–704. https://doi.org/10.1038/s41416-020-01059-1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Expert Report 2018. Height and birthweight and the risk of cancer. Available at Diet, Nutrition, Physical Activity and Cancer: a Global Perspective (wcrf.org).

  23. Nunney L. Size matters: height, cell number and a person’s risk of cancer. Proc Biol Sci. 1889;2018(285):20181743. https://doi.org/10.1098/rspb.2018.1743.

    Article  CAS  Google Scholar 

  24. Stefan N, Häring HU, Hu FB, Schulze MB. Divergent associations of height with cardiometabolic disease and cancer: epidemiology, pathophysiology, and global implications. Lancet Diabetes Endocrinol. 2016;4(5):457–67. https://doi.org/10.1016/S2213-8587(15)00474-X.

    Article  PubMed  Google Scholar 

  25. Gunnell D, Okasha M, Smith GD, Oliver SE, Sandhu J, Holly JM. Height, leg length, and cancer risk: a systematic review. Epidemiol Rev. 2001;23(2):313–42. https://doi.org/10.1093/oxfordjournals.epirev.a000809.

    Article  PubMed  CAS  Google Scholar 

  26. Murphy N, Carreras-Torres R, Song M, et al. Circulating levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 associate with risk of colorectal cancer based on serologic and mendelian randomization analyses. Gastroenterology. 2020;158(5):1300–1312.e20. https://doi.org/10.1053/j.gastro.2019.12.020.

    Article  PubMed  CAS  Google Scholar 

  27. Endogenous Hormones and Breast Cancer Collaborative Group, Key TJ, Appleby PN, Reeves GK, Roddam AW. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol. 2010;11(6):530–42. https://doi.org/10.1016/S1470-2045(10)70095-4.

    Article  CAS  Google Scholar 

  28. Schmidt JA, Allen NE, Almquist M, et al. Insulin-like growth factor-I and risk of differentiated thyroid carcinoma in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomark Prev. 2014;23(6):976–85. https://doi.org/10.1158/1055-9965.EPI-13-1210-T.

    Article  CAS  Google Scholar 

  29. Shi R, Berkel HJ, Yu H. Insulin-like growth factor-I and prostate cancer: a meta-analysis. Br J Cancer. 2001;85(7):991–6. https://doi.org/10.1054/bjoc.2001.1961.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Le Marchand L, Donlon T, Seifried A, Kaaks R, Rinaldi S, Wilkens LR. Association of a common polymorphism in the human GH1 gene with colorectal neoplasia. J Natl Cancer Inst. 2002;94(6):454–60. https://doi.org/10.1093/jnci/94.6.454.

    Article  PubMed  Google Scholar 

  31. Ma J, Pollak MN, Giovannucci E, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst. 1999;91(7):620–5. https://doi.org/10.1093/jnci/91.7.620.

    Article  PubMed  CAS  Google Scholar 

  32. Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med. 2011;3(70):70ra13. https://doi.org/10.1126/scitranslmed.3001845.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Laron Z, Kauli R, Lapkina L, Werner H. IGF-1 deficiency, longevity and cancer protection of patients with Laron syndrome. Mutat Res Rev Mutat Res. 2017;772:123–33. https://doi.org/10.1016/j.mrrev.2016.08.002.

    Article  PubMed  CAS  Google Scholar 

  34. Ikeno Y, Hubbard GB, Lee S, et al. Reduced incidence and delayed occurrence of fatal neoplastic diseases in growth hormone receptor/binding protein knockout mice. J Gerontol A Biol Sci Med Sci. 2009;64(5):522–9. https://doi.org/10.1093/gerona/glp017.

    Article  PubMed  CAS  Google Scholar 

  35. Harvey S. Extrapituitary growth hormone. Endocrine. 2010;38(3):335–59. https://doi.org/10.1007/s12020-010-9403-8.

    Article  PubMed  CAS  Google Scholar 

  36. Kasprzak A, Szaflarski W. Role of alternatively spliced messenger RNA (mRNA) isoforms of the insulin-like growth factor 1 (IGF1) in selected human tumors. Int J Mol Sci. 2020;21(19):6995. https://doi.org/10.3390/ijms21196995.

    Article  PubMed Central  CAS  Google Scholar 

  37. Lincoln DT, Sinowatz F, Temmim-Baker L, Baker HI, Kölle S, Waters MJ. Growth hormone receptor expression in the nucleus and cytoplasm of normal and neoplastic cells. Histochem Cell Biol. 1998;109(2):141–59. https://doi.org/10.1007/s004180050212.

    Article  PubMed  CAS  Google Scholar 

  38. Forbes BE, Blyth AJ, Wit JM. Disorders of IGFs and IGF-1R signaling pathways. Mol Cell Endocrinol. 2020;518:111035. https://doi.org/10.1016/j.mce.2020.111035.

    Article  PubMed  CAS  Google Scholar 

  39. Hakuno F, Takahashi SI. 40 years of IGF1: IGF1 receptor signaling pathways. J Mol Endocrinol. 2018;61(1):T69–86. https://doi.org/10.1530/JME-17-0311.

    Article  PubMed  CAS  Google Scholar 

  40. Bach LA. IGF-binding proteins. J Mol Endocrinol. 2018;61(1):T11–28. https://doi.org/10.1530/JME-17-0254.

    Article  PubMed  CAS  Google Scholar 

  41. Iams WT, Lovly CM. Molecular pathways: clinical applications and future direction of insulin-like growth factor-1 receptor pathway blockade. Clin Cancer Res. 2015;21(19):4270–7. https://doi.org/10.1158/1078-0432.CCR-14-2518.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Frank SJ. Classical and novel GH receptor signaling pathways. Mol Cell Endocrinol. 2020;518:110999. https://doi.org/10.1016/j.mce.2020.110999.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Lu M, Flanagan JU, Langley RJ, Hay MP, Perry JK. Targeting growth hormone function: strategies and therapeutic applications. Signal Transduct Target Ther. 2019;4:3. https://doi.org/10.1038/s41392-019-0036-y.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Li H, Batth IS, Qu X, et al. IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights. Mol Cancer. 2017;16(1):6. https://doi.org/10.1186/s12943-016-0576-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Sustarsic EG, Junnila RK, Kopchick JJ. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment. Biochem Biophys Res Commun. 2013;441(1):144–50. https://doi.org/10.1016/j.bbrc.2013.10.023.

    Article  PubMed  CAS  Google Scholar 

  46. Gebre-Medhin M, Kindblom LG, Wennbo H, Törnell J, Meis-Kindblom JM. Growth hormone receptor is expressed in human breast cancer. Am J Pathol. 2001;158(4):1217–22. https://doi.org/10.1016/S0002-9440(10)64071-0.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Wu ZS, Yang K, Wan Y, Qian PX, Perry JK, Chiesa J, Mertani HC, Zhu T, Lobie PE. Tumor expression of human growth hormone and human prolactin predict a worse survival outcome in patients with mammary or endometrial carcinoma. J Clin Endocrinol Metab. 2011;96(10):E1619–29. https://doi.org/10.1210/jc.2011-1245.

    Article  PubMed  CAS  Google Scholar 

  48. Buckels A, Zhang Y, Jiang J, Athar M, Afaq F, Shevde-Samant L, Frank SJ. Autocrine/paracrine actions of growth hormone in human melanoma cell lines. Biochem Biophys Rep. 2019;21:100716. https://doi.org/10.1016/j.bbrep.2019.100716.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Wu X, Liu F, Yao X, Li W, Chen C. Growth hormone receptor expression is up-regulated during tumorigenesis of human colorectal cancer. J Surg Res. 2007;143(2):294–9. https://doi.org/10.1016/j.jss.2007.03.056.

    Article  PubMed  CAS  Google Scholar 

  50. García-Caballero T, Mertani HM, Lambert A, Gallego R, Fraga M, Pintos E, Forteza J, Chevallier M, Lobie PE, Vonderhaar BK, Beiras A, Morel G. Increased expression of growth hormone and prolactin receptors in hepatocellular carcinomas. Endocrine. 2000;12(3):265–71. https://doi.org/10.1385/ENDO:12:3:265.

    Article  PubMed  Google Scholar 

  51. Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev. 2007;28(1):20–47. https://doi.org/10.1210/er.2006-0001.

    Article  PubMed  CAS  Google Scholar 

  52. Karagiannis A, Kassi E, Chatzigeorgiou A, Koutsilieris M. IGF bioregulation system in benign and malignant thyroid nodular disease: a systematic review. In Vivo. 2020;34(6):3069–91. https://doi.org/10.21873/invivo.12141.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Quinn KA, Treston AM, Unsworth EJ, et al. Insulin-like growth factor expression in human cancer cell lines. J Biol Chem. 1996;271(19):11477–83. https://doi.org/10.1074/jbc.271.19.11477.

    Article  PubMed  CAS  Google Scholar 

  54. Hellawell GO, Turner GD, Davies DR, Poulsom R, Brewster SF, Macaulay VM. Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease. Cancer Res. 2002;62(10):2942–50. PMID: 12019176.

    PubMed  CAS  Google Scholar 

  55. Messias de Lima CF, Dos Santos Reis MD, da Silva Ramos FW, Ayres-Martins S, Smaniotto S. Growth hormone modulates in vitro endothelial cell migration and formation of capillary-like structures. Cell Biol Int. 2017;41(5):577–84. https://doi.org/10.1002/cbin.10747.

    Article  PubMed  CAS  Google Scholar 

  56. Brunet-Dunand SE, Vouyovitch C, Araneda S, et al. Autocrine human growth hormone promotes tumor angiogenesis in mammary carcinoma. Endocrinology. 2009;150(3):1341–52. https://doi.org/10.1210/en.2008-0608.

    Article  PubMed  CAS  Google Scholar 

  57. Zhu T, Starling-Emerald B, Zhang X, et al. Oncogenic transformation of human mammary epithelial cells by autocrine human growth hormone. Cancer Res. 2005;65(1):317–24. PMID: 15665309.

    Article  PubMed  CAS  Google Scholar 

  58. Kopchick JJ, List EO, Kelder B, Gosney ES, Berryman DE. Evaluation of growth hormone (GH) action in mice: discovery of GH receptor antagonists and clinical indications. Mol Cell Endocrinol. 2014;386(1–2):34–45. https://doi.org/10.1016/j.mce.2013.09.004.

    Article  PubMed  CAS  Google Scholar 

  59. Clayton PE, Banerjee I, Murray PG, Renehan AG. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol. 2011;7(1):11–24. https://doi.org/10.1038/nrendo.2010.171.

    Article  PubMed  CAS  Google Scholar 

  60. Werner H, Laron Z. Role of the GH-IGF1 system in progression of cancer. Mol Cell Endocrinol. 2020;518:111003. https://doi.org/10.1016/j.mce.2020.111003.

    Article  PubMed  CAS  Google Scholar 

  61. Stochholm K, Johannsson G. Reviewing the safety of GH replacement therapy in adults. Growth Hormon IGF Res. 2015;25(4):149–57. https://doi.org/10.1016/j.ghir.2015.06.006.

    Article  CAS  Google Scholar 

  62. Stochholm K, Kiess W. Long-term safety of growth hormone-a combined registry analysis. Clin Endocrinol. 2018;88(4):515–28. https://doi.org/10.1111/cen.13502.

    Article  Google Scholar 

  63. Raman S, Grimberg A, Waguespack SG, et al. Risk of neoplasia in pediatric patients receiving growth hormone therapy--a report from the pediatric endocrine society drug and therapeutics committee. J Clin Endocrinol Metab. 2015;100(6):2192–203. https://doi.org/10.1210/jc.2015-1002.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Jenkins PJ, Mukherjee A, Shalet SM. Does growth hormone cause cancer? Clin Endocrinol. 2006;64(2):115–21. https://doi.org/10.1111/j.1365-2265.2005.02404.x.

    Article  CAS  Google Scholar 

  65. Chesnokova V, Zonis S, Barrett R, et al. Excess growth hormone suppresses DNA damage repair in epithelial cells. JCI Insight. 2019;4(3):e125762. https://doi.org/10.1172/jci.insight.125762.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Werner H. Tumor suppressors govern insulin-like growth factor signaling pathways: implications in metabolism and cancer. Oncogene. 2012;31(22):2703–14. https://doi.org/10.1038/onc.2011.447.

    Article  PubMed  CAS  Google Scholar 

  67. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90. https://doi.org/10.1016/j.cell.2009.11.007.

    Article  PubMed  CAS  Google Scholar 

  68. Xu XQ, Emerald BS, Goh EL, et al. Gene expression profiling to identify oncogenic determinants of autocrine human growth hormone in human mammary carcinoma. J Biol Chem. 2005;280(25):23987–4003. https://doi.org/10.1074/jbc.M503869200.

    Article  PubMed  CAS  Google Scholar 

  69. Mukhina S, Mertani HC, Guo K, Lee KO, Gluckman PD, Lobie PE. Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone. Proc Natl Acad Sci U S A. 2004;101(42):15166–71. https://doi.org/10.1073/pnas.0405881101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Graham TR, Zhau HE, Odero-Marah VA, et al. Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells [published correction appears in cancer res. 2008;68(10):4012]. Cancer Res. 2008;68(7):2479–88. https://doi.org/10.1158/0008-5472.CAN-07-2559.

    Article  PubMed  CAS  Google Scholar 

  71. Beppu K, Nakamura K, Linehan WM, Rapisarda A, Thiele CJ. Topotecan blocks hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression induced by insulin-like growth factor-I in neuroblastoma cells. Cancer Res. 2005;65(11):4775–81. https://doi.org/10.1158/0008-5472.CAN-04-3332.

    Article  PubMed  CAS  Google Scholar 

  72. Zhang Y, Liu Y, Wang L, Song H. The expression and role of trefoil factors in human tumors. Transl Cancer Res. 2019;8(4):1609–17. https://doi.org/10.21037/tcr.2019.07.48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Yusufu A, Shayimu P, Tuerdi R, Fang C, Wang F, Wang H. TFF3 and TFF1 expression levels are elevated in colorectal cancer and promote the malignant behavior of colon cancer by activating the EMT process. Int J Oncol. 2019;55(4):789–804. https://doi.org/10.3892/ijo.2019.4854.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Lin X, Zhang H, Dai J, et al. TFF3 contributes to epithelial-mesenchymal transition (EMT) in papillary thyroid carcinoma cells via the MAPK/ERK signaling pathway. J Cancer. 2018;9(23):4430–9. https://doi.org/10.7150/jca.24361.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Bergers G, Brekken R, McMahon G, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000;2(10):737–44. https://doi.org/10.1038/35036374.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Scheau C, Badarau IA, Costache R, et al. The role of matrix metalloproteinases in the epithelial-mesenchymal transition of hepatocellular carcinoma. Anal Cell Pathol (Amst). 2019;2019:9423907. https://doi.org/10.1155/2019/9423907.

    Article  CAS  Google Scholar 

  77. Malki A, ElRuz RA, Gupta I, Allouch A, Vranic S, Al Moustafa AE. Molecular mechanisms of colon cancer progression and metastasis: recent insights and advancements. Int J Mol Sci. 2020;22(1):130. https://doi.org/10.3390/ijms22010130.

    Article  PubMed Central  CAS  Google Scholar 

  78. Kong D, Zhou H, Neelakantan D, et al. VEGF-C mediates tumor growth and metastasis through promoting EMT-epithelial breast cancer cell crosstalk. Oncogene. 2020;40(5):964–79. https://doi.org/10.1038/s41388-020-01539-x.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Šelemetjev S, Ðoric I, Paunovic I, Tatic S, Cvejic D. Coexpressed high levels of VEGF-C and active MMP-9 are associated with lymphatic spreading and local invasiveness of papillary thyroid carcinoma. Am J Clin Pathol. 2016;146(5):594–602. https://doi.org/10.1093/ajcp/aqw184.

    Article  PubMed  CAS  Google Scholar 

  80. Drápela S, Bouchal J, Jolly MK, Culig Z, Souček K. ZEB1: a critical regulator of cell plasticity, DNA damage response, and therapy resistance. Front Mol Biosci. 2020;7:36. https://doi.org/10.3389/fmolb.2020.00036.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Masoud GN, Li W. HIF-1α pathway: role, regulation and intervention for cancer therapy. Acta Pharm Sin B. 2015;5(5):378–89. https://doi.org/10.1016/j.apsb.2015.05.007.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Osher E, Macaulay VM. Therapeutic targeting of the IGF axis. Cell. 2019;8(8):895. https://doi.org/10.3390/cells8080895.

    Article  CAS  Google Scholar 

  83. Evans A, Jamieson SM, Liu DX, Wilson WR, Perry JK. Growth hormone receptor antagonism suppresses tumour regrowth after radiotherapy in an endometrial cancer xenograft model. Cancer Lett. 2016;379(1):117–23. https://doi.org/10.1016/j.canlet.2016.05.031.

    Article  PubMed  CAS  Google Scholar 

  84. Minoia M, Gentilin E, Molè D, et al. Growth hormone receptor blockade inhibits growth hormone-induced chemoresistance by restoring cytotoxic-induced apoptosis in breast cancer cells independently of estrogen receptor expression. J Clin Endocrinol Metab. 2012;97(6):E907–16. https://doi.org/10.1210/jc.2011-3340.

    Article  PubMed  CAS  Google Scholar 

  85. Wu P, Nielsen TE, Clausen MH. Small-molecule kinase inhibitors: an analysis of FDA-approved drugs. Drug Discov Today. 2016;21(1):5–10. https://doi.org/10.1016/j.drudis.2015.07.008.

    Article  PubMed  CAS  Google Scholar 

  86. Friedbichler K, Hofmann MH, Kroez M, et al. Pharmacodynamic and antineoplastic activity of BI 836845, a fully human IGF ligand-neutralizing antibody, and mechanistic rationale for combination with rapamycin. Mol Cancer Ther. 2014;13(2):399–409. https://doi.org/10.1158/1535-7163.MCT-13-0598.

    Article  PubMed  CAS  Google Scholar 

  87. de Bono J, Lin CC, Chen LT, et al. Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours. Br J Cancer. 2020;122(9):1324–32. https://doi.org/10.1038/s41416-020-0774-1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Mustacchi P, Shimkin M. Occurrence of cancer in acromegaly and in hypopituitarism. Cancer. 1957;10(1):100–4. https://doi.org/10.1002/1097-0142(195701/02)10:1<100::aid-cncr2820100113>3.0.co;2-v.

    Article  PubMed  CAS  Google Scholar 

  89. Dal J, Leisner MZ, Hermansen K, Farkas DK, Bengtsen M, Kistorp C, Nielsen EH, Andersen M, Feldt-Rasmussen U, Dekkers OM, Sørensen HT, Jørgensen JOL. Cancer incidence in patients with acromegaly: a cohort study and meta-analysis of the literature. J Clin Endocrinol Metab. 2018;103(6):2182–8. https://doi.org/10.1210/jc.2017-02457.

    Article  PubMed  Google Scholar 

  90. Renehan AG, Brennan BM. Acromegaly, growth hormone and cancer risk. Best Pract Res Clin Endocrinol Metab. 2008;22(4):639–57. https://doi.org/10.1016/j.beem.2008.08.011.

    Article  PubMed  CAS  Google Scholar 

  91. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [published correction appears in CA Cancer J Clin. 2020;70(4):313]. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  92. Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary. 1999;2(1):29–41. https://doi.org/10.1023/a:1009965803750.

    Article  PubMed  CAS  Google Scholar 

  93. Reid TJ, Post KD, Bruce JN, Nabi Kanibir M, Reyes-Vidal CM, Freda PU. Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed. Clin Endocrinol. 2010;72(2):203–8. https://doi.org/10.1111/j.1365-2265.2009.03626.x.

    Article  Google Scholar 

  94. Boguszewski CL, Ayuk J. MANAGEMENT OF ENDOCRINE DISEASE: acromegaly and cancer: an old debate revisited. Eur J Endocrinol. 2016;175(4):R147–56. https://doi.org/10.1530/EJE-16-0178.

    Article  PubMed  CAS  Google Scholar 

  95. Terzolo M, Reimondo G, Berchialla P, et al. Acromegaly is associated with increased cancer risk: a survey in Italy. Endocr Relat Cancer. 2017;24(9):495–504. https://doi.org/10.1530/ERC-16-0553.

    Article  PubMed  Google Scholar 

  96. Ron E, Gridley G, Hrubec Z, Page W, Arora S, Fraumeni JF Jr. Acromegaly and gastrointestinal cancer [published correction appears in cancer 1992;69(2):549]. Cancer. 1991;68(8):1673–7. https://doi.org/10.1002/1097-0142(19911015)68:8<1673::aid-cncr2820680802>3.0.co;2-0.

    Article  PubMed  CAS  Google Scholar 

  97. Baris D, Gridley G, Ron E, et al. Acromegaly and cancer risk: a cohort study in Sweden and Denmark. Cancer Causes Control. 2002;13(5):395–400. https://doi.org/10.1023/a:1015713732717.

    Article  PubMed  CAS  Google Scholar 

  98. Petroff D, Tönjes A, Grussendorf M, et al. The incidence of cancer among acromegaly patients: results from the German acromegaly registry. J Clin Endocrinol Metab. 2015;100(10):3894–902. https://doi.org/10.1210/jc.2015-2372.

    Article  PubMed  CAS  Google Scholar 

  99. Popovic V, Damjanovic S, Micic D, et al. Increased incidence of neoplasia in patients with pituitary adenomas. Pituitary Study Group. Clin Endocrinol (Oxf). 1998;49(4):441–5. https://doi.org/10.1046/j.1365-2265.1998.00536.x.

    Article  CAS  Google Scholar 

  100. Cheng S, Gomez K, Serri O, Chik C, Ezzat S. The role of diabetes in acromegaly associated neoplasia. PLoS One. 2015;10(5):e0127276. https://doi.org/10.1371/journal.pone.0127276.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Wu JC, Huang WC, Chang HK, Ko CC, Lirng JF, Chen YC. Natural history of acromegaly: incidences, re-operations, cancers, and mortality rates in a national cohort. Neuroendocrinology. 2020;110(11–12):977–87. https://doi.org/10.1159/000505332.

    Article  PubMed  CAS  Google Scholar 

  102. Gullu BE, Celik O, Gazioglu N, Kadioglu P. Thyroid cancer is the most common cancer associated with acromegaly. Pituitary. 2010;13(3):242–8. https://doi.org/10.1007/s11102-010-0224-9.

    Article  PubMed  Google Scholar 

  103. Jenkins PJ. Acromegaly and cancer. Horm Res. 2004;62(Suppl 1):108–15. https://doi.org/10.1159/000080768.

    Article  PubMed  CAS  Google Scholar 

  104. Jass JR. Hyperplastic polyps and colorectal cancer: is there a link? Clin Gastroenterol Hepatol. 2004;2(1):1–8. https://doi.org/10.1016/s1542-3565(03)00284-2.

    Article  PubMed  Google Scholar 

  105. Cats A, Dullaart RP, Kleibeuker JH, et al. Increased epithelial cell proliferation in the colon of patients with acromegaly. Cancer Res. 1996;56(3):523–6. PMID: 8564965.

    PubMed  CAS  Google Scholar 

  106. Rokkas T, Pistiolas D, Sechopoulos P, Margantinis G, Koukoulis G. Risk of colorectal neoplasm in patients with acromegaly: a meta-analysis. World J Gastroenterol. 2008;14(22):3484–9. https://doi.org/10.3748/wjg.14.3484.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Jenkins PJ, Frajese V, Jones AM, et al. Insulin-like growth factor I and the development of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000;85(9):3218–21. https://doi.org/10.1210/jcem.85.9.6806.

    Article  PubMed  CAS  Google Scholar 

  108. Dworakowska D, Gueorguiev M, Kelly P, et al. Repeated colonoscopic screening of patients with acromegaly: 15-year experience identifies those at risk of new colonic neoplasia and allows for effective screening guidelines. Eur J Endocrinol. 2010;163(1):21–8. https://doi.org/10.1530/EJE-09-1080.

    Article  PubMed  CAS  Google Scholar 

  109. Terzolo M, Tappero G, Borretta G, et al. High prevalence of colonic polyps in patients with acromegaly. Influence of sex and age. Arch Intern Med. 1994;154(11):1272–6. PMID: 8203994.

    Article  PubMed  CAS  Google Scholar 

  110. Delhougne B, Deneux C, Abs R, Chanson P, Fierens H, Laurent-Puig P, Duysburgh I, Stevenaert A, Tabarin A, Delwaide J, Schaison G, Belaïche J, Beckers A. The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients. J Clin Endocrinol Metab. 1995;80(11):3223–6. https://doi.org/10.1210/jcem.80.11.7593429.

    Article  PubMed  CAS  Google Scholar 

  111. Colao A, Balzano A, Ferone D, et al. Increased prevalence of colonic polyps and altered lymphocyte subset pattern in the colonic lamina propria in acromegaly. Clin Endocrinol. 1997;47(1):23–8. https://doi.org/10.1046/j.1365-2265.1997.00253.x.

    Article  CAS  Google Scholar 

  112. Terzolo M, Reimondo G, Gasperi M, et al. Colonoscopic screening and follow-up in patients with acromegaly: a multicenter study in Italy. J Clin Endocrinol Metab. 2005;90(1):84–90. https://doi.org/10.1210/jc.2004-0240.

    Article  PubMed  CAS  Google Scholar 

  113. Renehan AG, Painter JE, Bell GD, Rowland RS, O’Dwyer ST, Shalet SM. Determination of large bowel length and loop complexity in patients with acromegaly undergoing screening colonoscopy. Clin Endocrinol. 2005;62(3):323–30. https://doi.org/10.1111/j.1365-2265.2005.02217.x.

    Article  Google Scholar 

  114. Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomark Prev. 2009;18(6):1688–94. https://doi.org/10.1158/1055-9965.EPI-09-0090.

    Article  Google Scholar 

  115. Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med. 1992;326(10):653–7. https://doi.org/10.1056/NEJM199203053261001.

    Article  PubMed  CAS  Google Scholar 

  116. Lincoln DT, Kaiser HE, Raju GP, Waters MJ. Growth hormone and colorectal carcinoma: localization of receptors. In Vivo. 2000;14(1):41–9. PMID: 10757060.

    PubMed  CAS  Google Scholar 

  117. Chesnokova V, Zonis S, Zhou C, et al. Growth hormone is permissive for neoplastic colon growth [published correction appears in proc Natl Acad sci U S a. 2016 Aug 30;113(35):E5251]. Proc Natl Acad Sci U S A. 2016;113(23):E3250–9. https://doi.org/10.1073/pnas.1600561113.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Dworakowska D, Grossman AB. Colonic cancer and acromegaly. Front Endocrinol (Lausanne). 2019;10:390. https://doi.org/10.3389/fendo.2019.00390.

    Article  Google Scholar 

  119. Mao YL, Li ZW, Lou CJ, Pang D, Zhang YQ. Phospho-STAT5 expression is associated with poor prognosis of human colonic adenocarcinoma. Pathol Oncol Res. 2011;17(2):333–9. https://doi.org/10.1007/s12253-010-9321-3.

    Article  PubMed  CAS  Google Scholar 

  120. Sekharam M, Zhao H, Sun M, et al. Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway. Cancer Res. 2003;63(22):7708–16. PMID: 14633695.

    PubMed  CAS  Google Scholar 

  121. Lahm H, Amstad P, Wyniger J, et al. Blockade of the insulin-like growth-factor-I receptor inhibits growth of human colorectal cancer cells: evidence of a functional IGF-II-mediated autocrine loop. Int J Cancer. 1994;58(3):452–9. https://doi.org/10.1002/ijc.2910580325.

    Article  PubMed  CAS  Google Scholar 

  122. Hakam A, Yeatman TJ, Lu L, et al. Expression of insulin-like growth factor-1 receptor in human colorectal cancer. Hum Pathol. 1999;30(10):1128–33. https://doi.org/10.1016/s0046-8177(99)90027-8.

    Article  PubMed  CAS  Google Scholar 

  123. Cascinu S, Del Ferro E, Grianti C, et al. Inhibition of tumor cell kinetics and serum insulin growth factor I levels by octreotide in colorectal cancer patients. Gastroenterology. 1997;113(3):767–72. https://doi.org/10.1016/s0016-5085(97)70170-7.

    Article  PubMed  CAS  Google Scholar 

  124. Bogazzi F, Russo D, Locci MT, et al. Apoptosis is reduced in the colonic mucosa of patients with acromegaly. Clin Endocrinol. 2005;63(6):683–8. https://doi.org/10.1111/j.1365-2265.2005.02405.x.

    Article  CAS  Google Scholar 

  125. Dutta P, Bhansali A, Vaiphei K, et al. Colonic neoplasia in acromegaly: increased proliferation or deceased apoptosis? Pituitary. 2012;15:166–73. https://doi.org/10.1007/s11102-011-0300-9.

    Article  PubMed  CAS  Google Scholar 

  126. Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933–51. https://doi.org/10.1210/jc.2014-2700.

    Article  PubMed  CAS  Google Scholar 

  127. Fleseriu M, Biller BMK, Freda PU, et al. A pituitary society update to acromegaly management guidelines. Pituitary. 2020;24(1):1–13. https://doi.org/10.1007/s11102-020-01091-7.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Giustina A, Barkan A, Beckers A, et al. A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J Clin Endocrinol Metab. 2020;105(4):dgz096. https://doi.org/10.1210/clinem/dgz096.

    Article  PubMed  Google Scholar 

  129. Tode B, Serio M, Rotella CM, et al. Insulin-like growth factor-I: autocrine secretion by human thyroid follicular cells in primary culture. J Clin Endocrinol Metab. 1989;69(3):639–47. https://doi.org/10.1210/jcem-69-3-639.

    Article  PubMed  CAS  Google Scholar 

  130. Tramontano D, Cushing GW, Moses AC, Ingbar SH. Insulin-like growth factor-I stimulates the growth of rat thyroid cells in culture and synergizes the stimulation of DNA synthesis induced by TSH and Graves’-IgG. Endocrinology. 1986;119(2):940–2. https://doi.org/10.1210/endo-119-2-940.

    Article  PubMed  CAS  Google Scholar 

  131. Chen Z, Jiang X, Feng Y, et al. Decrease in acromegaly-associated thyroid enlargement after normalization of IGF-1 levels: a prospective observation and in vitro study. Endocr Pract. 2020;26(4):369–77. https://doi.org/10.4158/EP-2019-0353.

    Article  PubMed  Google Scholar 

  132. Völzke H, Friedrich N, Schipf S, et al. Association between serum insulin-like growth factor-I levels and thyroid disorders in a population-based study. J Clin Endocrinol Metab. 2007;92(10):4039–45. https://doi.org/10.1210/jc.2007-0816.

    Article  PubMed  CAS  Google Scholar 

  133. Woliński K, Stangierski A, Gurgul E, et al. Thyroid lesions in patients with acromegaly - case-control study and update to the meta-analysis. Endokrynol Pol. 2017;68(1):2–6. https://doi.org/10.5603/EP.2017.0001.

    Article  PubMed  Google Scholar 

  134. Tita P, Ambrosio MR, Scollo C, et al. High prevalence of differentiated thyroid carcinoma in acromegaly. Clin Endocrinol. 2005;63(2):161–7. https://doi.org/10.1111/j.1365-2265.2005.02316.x.

    Article  Google Scholar 

  135. Kaldrymidis D, Papadakis G, Tsakonas G, et al. High incidence of thyroid cancer among patients with acromegaly. J BUON. 2016;21(4):989–93. PMID: 27685924.

    PubMed  Google Scholar 

  136. Tirosh A, Shimon I. Complications of acromegaly: thyroid and colon. Pituitary. 2017;20(1):70–5. https://doi.org/10.1007/s11102-016-0744-z.

    Article  PubMed  Google Scholar 

  137. Miyakawa M, Saji M, Tsushima T, Wakai K, Shizume K. Thyroid volume and serum thyroglobulin levels in patients with acromegaly: correlation with plasma insulin-like growth factor I levels. J Clin Endocrinol Metab. 1988;67(5):973–8. https://doi.org/10.1210/jcem-67-5-973.

    Article  PubMed  CAS  Google Scholar 

  138. Cheung NW, Boyages SC. The thyroid gland in acromegaly: an ultrasonographic study. Clin Endocrinol. 1997;46(5):545–9. https://doi.org/10.1046/j.1365-2265.1997.1680985.x.

    Article  CAS  Google Scholar 

  139. Uchoa HB, Lima GA, Corrêa LL, et al. Prevalence of thyroid diseases in patients with acromegaly: experience of a Brazilian center. Arq Bras Endocrinol Metabol. 2013;57(9):685–90. https://doi.org/10.1590/s0004-27302013000900003.

    Article  PubMed  Google Scholar 

  140. Wu X, Gao L, Guo X, et al. GH, IGF-1, and age are important contributors to thyroid abnormalities in patients with acromegaly. Int J Endocrinol. 2018;2018:6546832. https://doi.org/10.1155/2018/6546832.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Cannavò S, Squadrito S, Finocchiaro MD, et al. Goiter and impairment of thyroid function in acromegalic patients: basal evaluation and follow-up. Horm Metab Res. 2000;32(5):190–5. https://doi.org/10.1055/s-2007-978620.

    Article  PubMed  Google Scholar 

  142. Gasperi M, Martino E, Manetti L, et al. Prevalence of thyroid diseases in patients with acromegaly: results of an Italian multi-center study. J Endocrinol Investig. 2002;25(3):240–5. https://doi.org/10.1007/BF03343997.

    Article  CAS  Google Scholar 

  143. Mian C, Ceccato F, Barollo S, et al. AHR over-expression in papillary thyroid carcinoma: clinical and molecular assessments in a series of Italian acromegalic patients with a long-term follow-up. PLoS One. 2014;9(7):e101560. https://doi.org/10.1371/journal.pone.0101560.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Baştürk E, Kement M, Yavuzer D, et al. The role of insulin-like growth factor 1 in the development of benign and malignant thyroid nodules. Balkan Med J. 2012;29(2):133–8. https://doi.org/10.5152/balkanmedj.2011.034.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Liu YJ, Qiang W, Shi J, Lv SQ, Ji MJ, Shi BY. Expression and significance of IGF-1 and IGF-1R in thyroid nodules. Endocrine. 2013;44(1):158–64. https://doi.org/10.1007/s12020-012-9864-z.

    Article  PubMed  CAS  Google Scholar 

  146. Lawnicka H, Motylewska E, Borkowska M, et al. Elevated serum concentrations of IGF-1 and IGF-1R in patients with thyroid cancers. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2020;164(1):77–83. https://doi.org/10.5507/bp.2019.018.

    Article  PubMed  Google Scholar 

  147. Maiorano E, Ciampolillo A, Viale G, et al. Insulin-like growth factor 1 expression in thyroid tumors. Appl Immunohistochem Mol Morphol. 2000;8(2):110–9. https://doi.org/10.1097/00129039-200006000-00005.

    Article  PubMed  CAS  Google Scholar 

  148. Dagdelen S, Cinar N, Erbas T. Increased thyroid cancer risk in acromegaly. Pituitary. 2014;17(4):299–306. https://doi.org/10.1007/s11102-013-0501-5.

    Article  PubMed  Google Scholar 

  149. dos Santos MC, Nascimento GC, Nascimento AG, et al. Thyroid cancer in patients with acromegaly: a case-control study. Pituitary. 2013;16(1):109–14. https://doi.org/10.1007/s11102-012-0383-y.

    Article  PubMed  Google Scholar 

  150. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1–133. https://doi.org/10.1089/thy.2015.0020.

    Article  PubMed  PubMed Central  Google Scholar 

  151. Lai NB, Garg D, Heaney AP, Bergsneider M, Leung AM. No benefit of dedicated thyroid nodule screening in patients with acromegaly. Endocr Pract. 2020;26(1):16–21. https://doi.org/10.4158/EP-2019-0254.

    Article  PubMed  Google Scholar 

  152. Danilowicz K, Sosa S, Gonzalez Pernas MS, et al. Acromegaly and thyroid cancer: analysis of evolution in a series of patients. Clin Diabetes Endocrinol. 2020;6(1):24. https://doi.org/10.1186/s40842-020-00113-4.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363(9418):1346–53. https://doi.org/10.1016/S0140-6736(04)16044-3.

    Article  PubMed  CAS  Google Scholar 

  154. Nabarro JD. Acromegaly. Clin Endocrinol. 1987;26(4):481–512. https://doi.org/10.1111/j.1365-2265.1987.tb00805.x.

    Article  CAS  Google Scholar 

  155. Wolinski K, Stangierski A, Dyrda K, et al. Risk of malignant neoplasms in acromegaly: a case-control study. J Endocrinol Investig. 2017;40(3):319–22. https://doi.org/10.1007/s40618-016-0565-y.

    Article  CAS  Google Scholar 

  156. Bidosee M, Karry R, Weiss-Messer E, Barkey RJ. Growth hormone affects gene expression and proliferation in human prostate cancer cells. Int J Androl. 2011;34(2):124–37. https://doi.org/10.1111/j.1365-2605.2010.01064.x.

    Article  PubMed  CAS  Google Scholar 

  157. Wu J, Yu E. Insulin-like growth factor receptor-1 (IGF-IR) as a target for prostate cancer therapy. Cancer Metastasis Rev. 2014;33(2–3):607–17. https://doi.org/10.1007/s10555-013-9482-0.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Iwamura M, Sluss PM, Casamento JB, Cockett AT. Insulin-like growth factor I: action and receptor characterization in human prostate cancer cell lines. Prostate. 1993;22(3):243–52. https://doi.org/10.1002/pros.2990220307.

    Article  PubMed  CAS  Google Scholar 

  159. Nickerson T, Chang F, Lorimer D, Smeekens SP, Sawyers CL, Pollak M. In vivo progression of LAPC-9 and LNCaP prostate cancer models to androgen independence is associated with increased expression of insulin-like growth factor I (IGF-I) and IGF-1 receptor (IGF-IR). Cancer Res. 2001;61(16):6276–80. PMID: 11507082.

    PubMed  CAS  Google Scholar 

  160. Burfeind P, Chernicky CL, Rininsland F, Ilan J, Ilan J. Antisense RNA to the type I insulin-like growth factor receptor suppresses tumor growth and prevents invasion by rat prostate cancer cells in vivo. Proc Natl Acad Sci U S A. 1996;93(14):7263–8. https://doi.org/10.1073/pnas.93.14.7263.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Roddam AW, Allen NE, Appleby P, et al. Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann Intern Med. 2008;149(7):461–W88. https://doi.org/10.7326/0003-4819-149-7-200810070-00006.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Colao A, Marzullo P, Spiezia S, et al. Effect of growth hormone (GH) and insulin-like growth factor I on prostate diseases: an ultrasonographic and endocrine study in acromegaly, GH deficiency, and healthy subjects. J Clin Endocrinol Metab. 1999;84(6):1986–91. https://doi.org/10.1210/jcem.84.6.5776.

    Article  PubMed  CAS  Google Scholar 

  163. Colao A, Marzullo P, Ferone D, et al. Prostatic hyperplasia: an unknown feature of acromegaly. J Clin Endocrinol Metab. 1998;83(3):775–9. https://doi.org/10.1210/jcem.83.3.4645.

    Article  PubMed  CAS  Google Scholar 

  164. Watts EL, Goldacre R, Key TJ, Allen NE, Travis RC, Perez-Cornago A. Hormone-related diseases and prostate cancer: an English national record linkage study. Int J Cancer. 2020;147(3):803–10. https://doi.org/10.1002/ijc.32808.

    Article  PubMed  CAS  Google Scholar 

  165. Kim JH, Hong SK. Clinical utility of current biomarkers for prostate cancer detection. Investig Clin Urol. 2021;62(1):1–13. https://doi.org/10.4111/icu.20200395.

    Article  PubMed  CAS  Google Scholar 

  166. Lin C, Travis RC, Appleby PN, et al. Pre-diagnostic circulating insulin-like growth factor-I and bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2018;143(10):2351–8. https://doi.org/10.1002/ijc.31650.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000;21(3):215–44. https://doi.org/10.1210/edrv.21.3.0399.

    Article  PubMed  CAS  Google Scholar 

  168. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer. 2009;16(4):1103–23. https://doi.org/10.1677/ERC-09-0087.

    Article  PubMed  CAS  Google Scholar 

  169. Tsilidis KK, Kasimis JC, Lopez DS, Ntzani EE, Ioannidis JP. Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ. 2015;350:g7607. https://doi.org/10.1136/bmj.g7607.

    Article  PubMed  Google Scholar 

  170. Bansal D, Bhansali A, Kapil G, Undela K, Tiwari P. Type 2 diabetes and risk of prostate cancer: a meta-analysis of observational studies. Prostate Cancer Prostatic Dis. 2013;16(2):151–S1. https://doi.org/10.1038/pcan.2012.40.

    Article  PubMed  CAS  Google Scholar 

  171. Noto H, Tsujimoto T, Noda M. Significantly increased risk of cancer in diabetes mellitus patients: a meta-analysis of epidemiological evidence in Asians and non-Asians. J Diabetes Investig. 2012;3(1):24–33. https://doi.org/10.1111/j.2040-1124.2011.00183.x.

    Article  PubMed  Google Scholar 

  172. Lee J, Giovannucci E, Jeon JY. Diabetes and mortality in patients with prostate cancer: a meta-analysis. Springerplus. 2016;5(1):1548. https://doi.org/10.1186/s40064-016-3233-y.

    Article  PubMed  PubMed Central  Google Scholar 

  173. Chen Y, Wu F, Saito E, et al. Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia cohort consortium. Diabetologia. 2017;60(6):1022–32. https://doi.org/10.1007/s00125-017-4229-z.

    Article  PubMed  PubMed Central  Google Scholar 

  174. Sruthi CR, Raghu KG. Advanced glycation end products and their adverse effects: the role of autophagy. J Biochem Mol Toxicol. 2021;35:e22710. https://doi.org/10.1002/jbt.22710.

    Article  PubMed  CAS  Google Scholar 

  175. Harris IS, DeNicola GM. The complex interplay between antioxidants and ROS in cancer. Trends Cell Biol. 2020;30(6):440–51. https://doi.org/10.1016/j.tcb.2020.03.002.

    Article  PubMed  CAS  Google Scholar 

  176. Rojas A, González I, Morales E, Pérez-Castro R, Romero J, Figueroa H. Diabetes and cancer: looking at the multiligand/RAGE axis. World J Diabetes. 2011;2(7):108–13. https://doi.org/10.4239/wjd.v2.i7.108.

    Article  PubMed  PubMed Central  Google Scholar 

  177. Belfiore A, Malaguarnera R, Vella V, et al. Insulin receptor isoforms in physiology and disease: an updated view. Endocr Rev. 2017;38(5):379–431. https://doi.org/10.1210/er.2017-00073.

    Article  PubMed  PubMed Central  Google Scholar 

  178. Simpson A, Petnga W, Macaulay VM, Weyer-Czernilofsky U, Bogenrieder T. Insulin-like growth factor (IGF) pathway targeting in cancer: role of the IGF axis and opportunities for future combination studies. Target Oncol. 2017;12(5):571–97. https://doi.org/10.1007/s11523-017-0514-5.

    Article  PubMed  PubMed Central  Google Scholar 

  179. Livingstone C. IGF2 and cancer. Endocr Relat Cancer. 2013;20(6):R321–39. https://doi.org/10.1530/ERC-13-0231.

    Article  PubMed  CAS  Google Scholar 

  180. Brouwer-Visser J, Huang GS. IGF2 signaling and regulation in cancer. Cytokine Growth Factor Rev. 2015;26(3):371–7. https://doi.org/10.1016/j.cytogfr.2015.01.002.

    Article  PubMed  CAS  Google Scholar 

  181. Wang M, Yang Y, Liao Z. Diabetes and cancer: epidemiological and biological links. World J Diabetes. 2020;11(6):227–38. https://doi.org/10.4239/wjd.v11.i6.227.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Chen B, Li J, Chi D, et al. Non-coding RNAs in IGF-1R signaling regulation: the underlying pathophysiological link between diabetes and cancer. Cell. 2019;8(12):1638. https://doi.org/10.3390/cells8121638.

    Article  CAS  Google Scholar 

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  1. Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA

    Tamis Bright

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  1. Department of Neurological Surgery, University of San Francisco, San Francisco, CA, USA

    Lewis S. Blevins Jr.

  2. Department of Neurological Surgery, University of San Francisco, San Francisco, CA, USA

    Manish K. Aghi

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Bright, T. (2022). Acromegaly and Cancer. In: Blevins Jr., L.S., Aghi, M.K. (eds) Acromegaly. Contemporary Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-031-16258-9_10

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