Anthony J Swerdlow1,2, Rosie Cooke1, Dominique Beckers3,4, Birgit Borgström5, Gary Butler6,7, Jean-Claude Carel8,9, Stefano Cianfarani10,11, Peter Clayton12,13, Joël Coste14,15, Annalisa Deodati10, Emmanuel Ecosse14,15, Ruth Gausche16, Claudio Giacomozzi17, Anita C S Hokken-Koelega18,19, Aysha J Khan12,13, Wieland Kiess16, Claudia E Kuehni20, Primus-E Mullis21, Roland Pfaffle16, Lars Sävendahl11, Grit Sommer20, Muriel Thomas4, Anders Tidblad11, Sally Tollerfield6, Liesbet Van Eycken22, Gladys R J Zandwijken18,19. 1. Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP, United Kingdom. 2. Division of Breast Cancer Research, Institute of Cancer Research, London SW7 3RP, United Kingdom. 3. Unité d'Endocrinologie Pédiatrique, CHU NAMUR, Université Catholique de Louvain, 5530 Yvoir, Belgium. 4. Belgian Society for Pediatric Endocrinology and Diabetology, 1200 Brussels, Belgium. 5. Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, SE-141 86 Stockholm, Sweden. 6. University College London, Great Ormond Street Institute for Child Health, London WC1N 1EH, United Kingdom. 7. University College London Hospitals, National Health Service Foundation Trust, London NW1 2PG, United Kingdom. 8. Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert-Debré, Department of Pediatric Endocrinology and Diabetology, and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, F-75019 Paris, France. 9. PROTECT, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot, Sorbonne Paris Cité, F-75019 Paris, France. 10. Dipartimento Pediatrico Universitario Ospedaliero "Bambino Gesù" Children's Hospital-Tor Vergata University, 00165 Rome, Italy. 11. Department of Women's and Children's Health, Karolinska Institutet, SE-141 86 Stockholm, Sweden. 12. Royal Manchester Children's Hospital, Central Manchester University Hospitals, National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom. 13. School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester M13 9PL, United Kingdom. 14. Biostatistics and Epidemiology Unit, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, 1 Parvis Notre-Dame, 75004 Paris, France. 15. Equipe d'accueil 4360, University Paris Descartes, Sorbonne Paris Cité, 75005 Paris, France. 16. Hospital for Children and Adolescents and Centre of Pediatric Research, University of Leipzig, Liebigstr. 20a, D-04103 Leipzig, Germany. 17. Centre for Pediatric Endocrinology and Diabetes, Pediatric Unit, Carlo Poma Hospital, 46100 Mantua, Italy. 18. Dutch Growth Research Foundation, Westzeedijk 106, 3016 AH Rotterdam, The Netherlands. 19. Department of Pediatrics, Subdivision of Endocrinology, Erasmus Medical Center/Sophia Children's Hospital, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. 20. Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, 3012 Bern, Switzerland. 21. Division of Paediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital Bern, Inselspital, 3010 Bern, Switzerland. 22. Belgian Cancer Registry, Department Research, Koningsstraat 215, Box 7-B-1210 Brussels, Belgium.
Abstract
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.
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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