Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study

被引:107
作者
Swerdlow, Anthony J [1 ,2 ]
Cooke, Rosie G [1 ]
Beckers, Dominique D [3 ,4 ]
Borgstrom, Birgit E [5 ]
Butler, Gary B [6 ,7 ]
Carel, Jean-Claude C [8 ,9 ,10 ]
Cianfarani, Stefano E [11 ,12 ]
Clayton, Peter G [13 ,14 ]
Coste, Joel A [15 ,16 ]
Deodati, Annalisa C [11 ]
Ecosse, Emmanuel K [15 ,16 ]
Gausche, Ruth B [17 ,18 ]
Giacomozzi, Claudio E [19 ,20 ]
Hokken-Koelega, Anita C [21 ,22 ]
Khan, Aysha J [13 ,14 ]
Kiess, Wieland B [17 ,18 ]
Kuehni, Claudia E [23 ]
Mullis, Primus-E. C [24 ]
Pfaffle, Roland L [17 ,18 ]
Savendahl, Lars [12 ]
Sommer, Grit L
Thomas, Muriel K [4 ]
Tidblad, Anders M [12 ]
Tollerfield, Sally L [6 ]
Van Eycken, Liesbet D [25 ]
Zandwijken, Gladys R [21 ,22 ]
机构
[1] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England
[2] Inst Canc Res, Div Breast Canc Res, London SW7 3RP, England
[3] Catholic Univ Louvain, CHU NAMUR, Unite Endocrinol Pediatr, B-5530 Yvoir, Belgium
[4] Belgian Soc Pediat Endocrinol & Diabetol, B-1200 Brussels, Belgium
[5] Karolinska Inst, Dept Clin Sci Intervent & Technol, SE-14186 Stockholm, Sweden
[6] UCL, Great Ormond St Inst Child Hlth, London WC1N 1EH, England
[7] Univ Coll London Hosp, Natl Hlth Serv Fdn, London NW1 2PG, England
[8] Hop Univ Robert Debre, AP HP, Dept Pediat Endocrinol & Diabetol, F-75019 Paris, France
[9] Ctr Reference Malad Endocriniennes Rares Croissan, F-75019 Paris, France
[10] Univ Paris Diderot, INSERM, PROTECT, Sorbonne Paris Cite, F-75019 Paris, France
[11] Univ Ospedaliero Bambino Gesu, Childrens Hospital, Dipartimento Pediat, I-00165 Rome, Italy
[12] Karolinska Inst, Dept Womens & Childrens Hlth, SE-14186 Stockholm, Sweden
[13] Cent Manchester Univ Hosp, Manchester Acad Hlth Sci Ctr, Natl Hlth Serv Fdn Trust, Royal Manchester Childrens Hosp, Manchester M13 9WL, Lancs, England
[14] Sch Med Sci, Fac Biol Med & Hlth, Manchester M13 9PL, Lancs, England
[15] AP HP, Hotel Dieu, Biostat & Epidemiol Unit, 1 Parvis Notre Dame, F-75004 Paris, France
[16] Univ Paris 05, Equipe Daccueil 4360, Sorbonne Paris Cite, F-75005 Paris, France
[17] Univ Leipzig, Hosp Children & Adolescents, Liebigstr 20a, D-04103 Leipzig, Germany
[18] Univ Leipzig, Ctr Pediat Res, Liebigstr 20a, D-04103 Leipzig, Germany
[19] Carlo Poma Hosp, Ctr Pediat Endocrinol, I-46100 Mantua, Italy
[20] Carlo Poma Hosp, Diabet Pediat Unit, I-46100 Mantua, Italy
[21] Dutch Growth Res Fdn, Westzeedijk 106, NL-3016 AH Rotterdam, Netherlands
[22] Sophia Childrens Univ Hosp, Erasmus Med Center, Dept Pediat, Subdiv Endocrinol, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands
[23] Univ Bern, Inst Soc & Prevent Med, Finkenhubelweg 11, CH-3012 Bern, Switzerland
[24] Univ Childrens Hosp Bern, Inselspital, Div Paediat Endocrinol Diabetol & Metabolism, CH-3010 Bern, Switzerland
[25] Belgian Canc Registry, Dept Res, Koningsstraat 215,Box 7, B-1210 Brussels, Belgium
基金
瑞典研究理事会;
关键词
GH-DEFICIENT ADULTS; LONG-TERM SAFETY; 2ND NEOPLASMS; MORTALITY; REPLACEMENT; THERAPY; LEUKEMIA; INCREASE; DISEASE;
D O I
10.1210/jc.2016-2046
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1661 / 1672
页数:12
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