The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study
Open accessAbstract
Context: Growth hormone (GH) is prescribed for an increasing range of indications, but there has been concern that it might raise cancer risk. Published data are limited. Objective: To examine cancer risks in relation to GH treatment. Design: Cohort study. Setting: Population-based. Patients: Cohort of 23,984 patients treated with recombinant human GH (r-hGH) in eight European countries since this treatment was first used in 1984. Cancer expectations from country-specific national population statistics. Main Outcome Measures: Cancer incidence and cancer mortality. Results: Incidence and mortality risks in the cohort were raised for several cancer sites, largely consequent on second primary malignancies in patients given r-hGH after cancer treatment. There was no clear raised risk in patients with growth failure without other major disease. Only for bone and bladder cancers was incidence significantly raised in GH-treated patients without previous cancer. Cancer risk was unrelated to duration or cumulative dose of r-hGH treatment, but for patients treated after previous cancer, cancer mortality risk increased significantly with increasing daily r-hGH dose (P trend < 0.001). Hodgkin lymphoma (HL) incidence increased significantly with longer follow-up (P trend = 0.001 for patients overall and 0.002 for patients without previous cancer). Conclusions: Our results do not generally support a carcinogenic effect of r-hGH, but the unexplained trend in cancer mortality risk in relation to GH dose in patients with previous cancer, and the indication of possible effects on bone cancer, bladder cancer, and HL risks, need further investigation.
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“data from GH registries provide no evidence of an increase in risk of neoplasia with treatment.173,208,222-224”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [223]
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“For the three cancer sites for which there is most published support for an association with IGF-1 levels— colorectum, breast, and prostate (2)—the evidence from our cohort and previously (9, 10, 18, 19) is too sparse to reach a conclusion on relations to GH treatment, reflecting the rarity of these cancers at childho…”
BackgroundSklar, C. A., Mertens, A. C., Mitby, P. A., Occhiogrosso, G., Qin, J., Heller, G., Yasui, Y., & Robison, L. L. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.7.8606 · Cited by 307
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“, neurofibromatosis) that lead to GH therapy are themselves strong predisposing factors for cancer, we followed previous practice (11, 12, 16) in excluding individuals with such conditions (listed in Supplemental Data) from analysis.”
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Growth Hormone Treatment and Risk of Second Neoplasms in the Childhood Cancer Survivor
Ergun-Longmire, B., Mertens, A. C., Mitby, P. A., Qin, J., Heller, G., Shi, W., Yasui, Y., Robison, L. L., & Sklar, C. A. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0656 · Cited by 272 · cited 4×
“Potential effects on leukemia (5, 6) and other malignancy (1) risks have been suggested, and second primary malignancy risk has been shown raised in patients receiving GH after childhood cancer (7, 8).”
BackgroundInfluentialSvensson, J., Bengtsson, B. ‐., Rosén, T., Odén, A., & Johannsson, G. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031601 · Cited by 236
Mortality and Cancer Incidence in Acromegaly: A Retrospective Cohort Study
Orme, S., McNally, R., Cartwright, R. A., & Belchetz, P. E. (1999) · The Journal of Urology · doi:10.1016/s0022-5347(01)61691-4 · Cited by 227
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“Melanoma, however, is not a tumor usually raised after radiotherapy and chemotherapy, although it has been in at least one instance (31).”
BackgroundCancer incidence in women with Turner syndrome in Great Britain: a national cohort study
Schoemaker, M. J., Swerdlow, A. J., Higgins, C. D., Wright, A. F., & Jacobs, P. A. (2008) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70033-0 · Cited by 202
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Mortality and Cancer Incidence in Acromegaly: A Retrospective Cohort Study
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Patterson, B. C., Chen, Y., Sklar, C. A., Neglia, J. P., Yasui, Y., Mertens, A. C., Armstrong, G. T., Meadows, A. T., Stovall, M., Robison, L. L., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4159 · Cited by 144 · cited 2×
“Only for CNS tumors are there previous data on risks as a second malignancy after GH, with no raised risk relating to GH (25).”
Backgroundvan Bunderen, C. C., van Nieuwpoort, I. C., Arwert, L. I., Heymans, M. W., Franken, A. A. M., Koppeschaar, H. P. F., van der Lely, A. J., & Drent, M. L. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1215 · Cited by 132 · cited 1×
“Previous large r-hGH cohorts, with one exception (16), have censored follow-up at last clinic visit, not at a fixed end-date (10, 12, 13, 26).”
BackgroundOverall and cause-specific mortality in GH-deficient adults on GH replacement
Gaillard, R. C., Mattsson, A. F., Åkerblad, A., Bengtsson, B., Cara, J. F., Feldt‐Rasmussen, U., Kołtowska‐Häggström, M., Monson, J. P., Saller, B., Wilton, P., et al. (2012) · European Journal of Endocrinology · doi:10.1530/eje-11-1028 · Cited by 130 · cited 2×
“Previous large r-hGH cohorts, with one exception (16), have censored follow-up at last clinic visit, not at a fixed end-date (10, 12, 13, 26).”
BackgroundMortality and GH deficiency: a nationwide study
Stochholm, K., Gravholt, C. H., Laursen, T., Laurberg, P., Andersen, M., Kristensen, L. Ø., Feldt‐Rasmussen, U., Christiansen, J. S., Frydenberg, M., & Green, A. (2007) · European Journal of Endocrinology · doi:10.1530/eje-07-0013 · Cited by 129 · cited 1×
“This is clearest for patients receiving GH because of malignancy or chromosomal instability syndromes, but applies to some extent to virtually every underlying diagnosis, for example, hypopituitarism (9, 22) or Turner syndrome (23).”
BackgroundLong-term mortality in the United States cohort of pituitary-derived growth hormone recipients
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“Our follow-up for mortality and cancer incidence, like that in the p-hGH cohorts (18, 19), was to a fixed end-date, and had high completeness through routine national data systems (15).”
BackgroundMethodInfluentialHeight at diagnosis and birth-weight as risk factors for osteosarcoma
Mirabello, L., Pfeiffer, R., Murphy, G., Daw, N. C., Patiño-Garcia, A., Troisi, R. J., Hoover, R. N., Douglass, C., Schüz, J., Craft, A. W., et al. (2011) · Cancer Causes & Control · doi:10.1007/s10552-011-9763-2 · Cited by 116 · cited 1×
“There was no evidence in our data that bone cancer risk was related to GH dose, but the significant bone cancer excess in both cancer and noncancer patients, and the anatomical and age distributions of bone cancer and association with height in the general population (28), argue that the relation needs reexamination i…”
BackgroundRecent Status in the Occurrence of Leukemia in Growth Hormone-Treated Patients in Japan
Nishi, Y., Tanaka, T., Takano, K., Fujieda, K., Igarashi, Y., Hanew, K., Hirano, T., Yokoya, S., Tachibana, K., Saito, T., et al. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.6.5716 · Cited by 113
Risk of Leukemia After Treatment With Pituitary Growth Hormone
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“The large postmarketing surveillance studies (10 – 12, 14, 16) have also depended on active reporting of cancers to the pharmaceutical company by physicians, the completeness of which is unknown, especially after patients leave pediatric endocrine care.”
BackgroundTuffli, G. A., Johanson, A. J., Rundle, A. C., & Allen, D. B. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.4.7714117 · Cited by 84 · cited 2×
“, neurofibromatosis) that lead to GH therapy are themselves strong predisposing factors for cancer, we followed previous practice (11, 12, 16) in excluding individuals with such conditions (listed in Supplemental Data) from analysis.”
BackgroundMethodLong-Term Safety of Growth Hormone Replacement after CNS Irradiation
Mackenzie, S. D., Craven, T., Gattamaneni, H. R., Swindell, R., Shalet, S. M., & Brabant, G. E. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0112 · Cited by 83 · cited 1×
“of a few hundred GH-treated cancer patients (7, 20).”
BackgroundSwerdlow, A. J., Cooke, R., Albertsson-Wikland, K. G., Borgström, B., Butler, G. E., Cianfarani, S., Clayton, P., Coste, J., Deodati, A., Écosse, E., et al. (2015) · Hormone Research in Paediatrics · doi:10.1159/000435856 · Cited by 62 · cited 12×
“Cancer incidence follow-up based on cancer registration was highly complete in Belgium, the Netherlands, Sweden, Switzerland, and the United Kingdom, but less complete in France, Germany, and Italy, where there was no national cancer registration.”
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“For the three cancer sites for which there is most published support for an association with IGF-1 levels— colorectum, breast, and prostate (2)—the evidence from our cohort and previously (9, 10, 18, 19) is too sparse to reach a conclusion on relations to GH treatment, reflecting the rarity of these cancers at childho…”
BackgroundDeodati, A., Ferroli, B. B., & Cianfarani, S. (2014) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2014.02.001 · Cited by 46 · cited 1×
“Potential effects on leukemia (5, 6) and other malignancy (1) risks have been suggested, and second primary malignancy risk has been shown raised in patients receiving GH after childhood cancer (7, 8).”
BackgroundDoes growth hormone therapy increase the risk of cancer?
Swerdlow, A. J. (2006) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0295 · Cited by 19 · cited 2×
“Potential effects on leukemia (5, 6) and other malignancy (1) risks have been suggested, and second primary malignancy risk has been shown raised in patients receiving GH after childhood cancer (7, 8).”
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Growth hormone — past, present and future
Ranke, M. B., & Wit, J. M. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2018.22 · Cited by 362
Turner syndrome: mechanisms and management
Gravholt, C. H., Viuff, M. H., Brun, S., Stochholm, K., & Andersen, N. H. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0224-4 · Cited by 356
Lilienthal, I., & Herold, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186885 · Cited by 300
“Furthermore, children treated with GH have been found to have an increased incidence of osteosarcoma [30].”
BackgroundClinical practice guidelines for the care of girls and women with Turner syndrome.
Gravholt, C. H., Andersen, N. H., Christin-Maitre, S., Davis, S. M., Duijnhouwer, A., Gawlik, A., Maciel-Guerra, A. T., Gutmark-Little, I., Fleischer, K., Hong, D., et al. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae050 · Cited by 224
Hokken-Koelega, A., van der Steen, M., Boguszewski, M. C. D. S., Cianfarani, S., Dahlgren, J., Horikawa, R., Verónica Mericq, G., Rapaport, R., Al-Herbish, A. S., Braslavsky, D. G., et al. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad002 · Cited by 208
Metadata
- Authors
- Swerdlow, A. J., Cooke, R., Beckers, D., Borgström, B., Butler, G., Carel, J.-C., Cianfarani, S., Clayton, P., Coste, J., Deodati, A., Ecosse, E., Gausche, R., Giacomozzi, C., Hokken-Koelega, A. C. S., Khan, A. J., Kiess, W., Kuehni, C. E., Mullis, P.-E., Pfaffle, R., Sävendahl, L., Sommer, G., Thomas, M., Tidblad, A., Tollerfield, S., Van Eycken, L., & Zandwijken, G. R. J.
- Affiliations
- Institute of Cancer Research (GB)
- UCLouvain (BE)
- Karolinska Institutet (SE)
- National Health Service (GB)
- Inserm (FR)
- University of Rome Tor Vergata (IT)
- Leipzig University (DE)
- Azienda Ospedaliera Carlo Poma (IT)
- Erasmus MC (NL)
- University of Bern (CH)
- University Hospital of Bern (CH)
- University College London (GB)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2017-02-10
- Volume
- 102
- Issue
- 5
- Pages
- 1661-1672
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC6061931
- OpenAlex
- W2597357044
- Cited by
- 153
- References
- 31
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 16 · 2023: 14 · 2022: 23 · 2021: 16 · 2020: 19 · 2019: 26 · 2018: 18 · 2017: 6
- FWCI
- 14.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion, cc-by)
- Digital Access to Libraries (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- Open Access CRIS of the University of Bern
- Funders
- Eli Lilly and Company
- Pfizer
- University College London
- European Commission (223497)
- Cancerfonden
- Novo Nordisk
- Vetenskapsrådet
- Barncancerfonden
- Institut National Du Cancer
- Agence Française de Sécurité Sanitaire des Produits de Santé
- Ipsen
- Novo Nordisk Pharma
- FP7 Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Keywords
- recombinant human growth hormone, cancer risk, second primary malignancy, cancer mortality, cancer incidence, Hodgkin's disease, bone cancer, bladder cancer, growth hormone dose
- MeSH terms
- Adolescent, Urinary Bladder Neoplasms, Bone Diseases, Developmental, Bone Neoplasms, Child, Child, Preschool, Dose-Response Relationship, Drug, Europe, Female, Growth Disorders, Hodgkin Disease, Humans, Hypopituitarism, Infant, Infant, Newborn, Male, Neoplasms, Recombinant Proteins, Risk, Turner Syndrome, Cohort Studies, Incidence, Neoplasms, Second Primary, Human Growth Hormone, Renal Insufficiency, Chronic, Young Adult
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