Occurrence of neoplasms in individuals with congenital, severe GH deficiency from the Itabaianinha kindred

Marinho, Cindi G.; Mermejo, Lívia Mara; Salvatori, Roberto; Assirati, João Alberto; Oliveira, Carla R. P.; Santos, Elenilde G.; Leal, Ângela Cristina Gomes Borges; Barros-Oliveira, Cynthia S; Damascena, Nicole Prata; Lima, Carlos Anselmo; Farias, Catarine T.; Moreira, Ayrton Custódio; Aguiar‐Oliveira, Manuel H.

doi:10.1016/j.ghir.2018.03.004

Cited by 15 publications

(7 citation statements)

References 26 publications

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“…Similarly, low malignancy risk has been reported in an Israeli Laron syndrome cohort (42,43). Cancer rates are also low but not completely absent in a Brazilian cohort of individuals with isolated congenital GHD due to a GHRH-receptor gene mutation, who have very low, but detectable, serum levels of GH and IGF-I (44).…”

Section: What Is the Role Of Gh-igf-i In Tumour Genesis? Epidemiologymentioning

confidence: 57%

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Boguszewski

Chemaililly

et al. 2022

European Journal of Endocrinology

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Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.

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Section: What Is the Role Of Gh-igf-i In Tumour Genesis? Epidemiologymentioning

confidence: 57%

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Boguszewski

Chemaililly

et al. 2022

European Journal of Endocrinology

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“…In humans, congenital GHD or GH resistance (Laron dwarfism) have been associated with a lower incidence of malignancies, similarly to what is observed in animal models [67][68][69]. Cells treated with serum obtained from Ecuadorian patients with Laron syndrome have been shown to exhibit reduced DNA breaks and increased apoptosis [68].…”

Section: Igfbp-3 Igf II Receptormentioning

confidence: 79%

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

et al. 2021

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Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

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“…Individuals with GHR deficiency (GHRD) caused by genetic mutations in the displayed GHR gene and congenital IGF1 appear to be protected against the development of neoplasms. This protection, although also well documented, is not absolute in IGHD, GHD associated with multiple pituitary defects and GHRH receptor deficiency ( Shevah and Laron, 2007 ; Guevara-Aguirre et al, 2011 ; Steuerman et al, 2011 ; Marinho et al, 2018 ).…”

Section: Role Of Gh-igf1 Signaling In Variant Cancersmentioning

confidence: 91%

Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers

Cheng

Gui

et al. 2021

Front. Cell Dev. Biol.

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Radiotherapy remains one of the most important cancer treatment modalities. In the course of radiotherapy for tumor treatment, the incidental irradiation of adjacent tissues could not be completely avoided. DNA damage is one of the main factors of cell death caused by ionizing radiation, including single-strand (SSBs) and double-strand breaks (DSBs). The growth hormone-Insulin-like growth factor 1 (GH-IGF1) axis plays numerous roles in various systems by promoting cell proliferation and inhibiting apoptosis, supporting its effects in inducing the development of multiple cancers. Meanwhile, the GH-IGF1 signaling involved in DNA damage response (DDR) and DNA damage repair determines the radio-resistance of cancer cells subjected to radiotherapy and repair of adjacent tissues damaged by radiotherapy. In the present review, we firstly summarized the studies on GH-IGF1 signaling in the development of cancers. Then we discussed the adverse effect of GH-IGF1 signaling in radiotherapy to cancer cells and the favorable impact of GH-IGF1 signaling on radiation damage repair to adjacent tissues after irradiation. This review further summarized recent advances on research into the molecular mechanism of GH-IGF1 signaling pathway in these effects, expecting to specify the dual characters of GH-IGF1 signaling pathways in radiotherapy and post-radiotherapy repair of cancers, subsequently providing theoretical basis of their roles in increasing radiation sensitivity during cancer radiotherapy and repairing damage after radiotherapy.

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Occurrence of neoplasms in individuals with congenital, severe GH deficiency from the Itabaianinha kindred

Cited by 15 publications

References 26 publications

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers

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