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      Is Open Access

      Risk of cancer in patients treated with recombinant human growth hormone in childhood

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Recombinant human growth hormone (GH) has been in use for over 30 years, and its indications have gradually expanded from the classical replacement therapy in GH deficiency (GHD) to pharmacological therapy in patients with normal GH secretion. The insulin-like growth factor-I (IGF-I ) is closely GH dependent and is the effector of GH biological actions in peripheral tissues. Since IGF-I has potent mitogenic and antiapoptotic effects, the use of GH, especially outside GHD, has raised safety concern regarding cancer risk. The results of experimental, epidemiological and observational studies are not univocal and a number of biases and confounders affect the interpretation of data. The aim of this review is to critically review the data linking GH therapy during childhood with cancer risk, highlighting strengths and weaknesses of the available evidence.

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          Insulin-like growth factors and their binding proteins: biological actions.

          D Clemmons, J Jones (1995)
          Article 0 comments Cited 366 times – based on 0 reviews     Review now
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            Role of insulin-like growth factors in embryonic and postnatal growth.

            Julie Baker, Jeh-Ping Liu, Elizabeth J. Robertson … (1993)
            A developmental analysis of growth kinetics in mouse embryos carrying null mutations of the genes encoding insulin-like growth factor I (IGF-I), IGF-II, and the type 1 IGF receptor (IGF1R), alone or in combination, defined the onset of mutational effects leading to growth deficiency and indicated that between embryonic days 11.0 and 12.5, IGF1R serves only the in vivo mitogenic signaling of IGF-II. From E13.5 onward, IGF1R interacts with both IGF-I and IGF-II, while IGF-II recognizes an additional unknown receptor (XR). In contrast with the embryo proper, placental growth is served exclusively by an IGF-II-XR interaction. Additional genetic data suggested that the type 2IGF/mannose 6-phosphate receptor is an unlikely candidate for XR. Postnatal growth curves indicated that surviving Igf-1(-/-) mutants, which are infertile and exhibit delayed bone development, continue to grow with a retarded rate after birth in comparison with wild-type littermates and become 30% of normal weight as adults.
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              Circulating concentrations of insulin-like growth factor-I and risk of breast cancer.

              S E Hankinson, W Willett, G. A. Colditz … (1998)
              Insulin-like growth factor (IGF)-I, a mitogenic and antiapoptotic peptide, can affect the proliferation of breast epithelial cells, and is thought to have a role in breast cancer. We hypothesised that high circulating IGF-I concentrations would be associated with an increased risk of breast cancer. We carried out a nested case-control study within the prospective Nurses' Health Study cohort. Plasma concentrations of IGF-I and IGF binding protein 3 (IGFBP-3) were measured in blood samples collected in 1989-90. We identified 397 women who had a diagnosis of breast cancer after this date and 620 age-matched controls. IGF-I concentrations were compared by logistic regression with adjustment for other breast-cancer risk factors. There was no association between IGF-I concentrations and breast-cancer risk among the whole study group. In postmenopausal women there was no association between IGF-I concentrations and breast-cancer risk (top vs bottom quintile of IGF-I, relative risk 0.85 [95% CI 0.53-1.39]). The relative risk of breast cancer among premenopausal women by IGF-I concentration (top vs bottom tertile) was 2.33 (1.06-5.16; p for trend 0.08). Among premenopausal women less than 50 years old at the time of blood collection, the relative risk was 4.58 (1.75-12.0; p for trend 0.02). After further adjustment for plasma IGFBP-3 concentrations these relative risks were 2.88 and 7.28, respectively. A positive relation between circulating IGF-I concentration and risk of breast cancer was found among premenopausal but not postmenopausal women. Plasma IGF-I concentrations may be useful in the identification of women at high risk of breast cancer and in the development of risk reduction strategies. Additional larger studies of this association among premenopausal women are needed to provide more precise estimates of effect.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Ann Pediatr Endocrinol Metab
                Journal ID (iso-abbrev): Ann Pediatr Endocrinol Metab
                Journal ID (publisher-id): APEM
                Title: Annals of Pediatric Endocrinology & Metabolism
                Publisher: Korean Society of Pediatric Endocrinology
                ISSN (Print): 2287-1012
                ISSN (Electronic): 2287-1292
                Publication date (Print): June 2019
                Publication date (Electronic): 30 June 2019
                Volume: 24
                Issue: 2
                Pages: 92-98
                Affiliations
                [1 ]Dipartimento Pediatrico Universitario Ospedaliero, “Bambino Gesù” Children’s Hospital – Tor Vergata University, Rome, Italy
                [2 ]Department of Women’s and Children’s Health, Karolinska Institutet and University Hospital, Stockholm, Sweden
                Author notes
                Address for correspondence: Stefano Cianfarani, MD, PhD Dipartimento Pediatrico Universitario Ospedaliero, “Bambino Gesù” Children’s Hospital–Tor Vergata University, Piazza S. Onofrio 4, 00165-Rome, Italy Tel: +39-06-6859-3074 Fax: +39-06-6859-2508 E-mail: stefano.cianfarani@ 123456uniroma2.it
                Author information
                http://orcid.org/0000-0002-6065-8328
                Article
                Publisher ID: apem-2019-24-2-92
                DOI: 10.6065/apem.2019.24.2.92
                PMC ID: 6603614
                PubMed ID: 31261472
                SO-VID: 5082c4b1-0ab0-4eed-911d-091ae3e0a0b2
                Copyright © © 2019 Annals of Pediatric Endocrinology & Metabolism
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 5 June 2019
                Date accepted : 13 June 2019
                Categories
                Subject: Review Article

                Keywords: growth hormone,insulin-like growth factor,cancer
                Data availability:
                Keywords: growth hormone, insulin-like growth factor, cancer

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