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

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.

SUBMITTER: Swerdlow AJ

PROVIDER: S-EPMC6061931 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Swerdlow Anthony J AJ Cooke Rosie R Beckers Dominique D Borgström Birgit B Butler Gary G Carel Jean-Claude JC Cianfarani Stefano S Clayton Peter P Coste Joël J Deodati Annalisa A Ecosse Emmanuel E Gausche Ruth R Giacomozzi Claudio C Hokken-Koelega Anita C S ACS Khan Aysha J AJ Kiess Wieland W Kuehni Claudia E CE Mullis Primus-E PE Pfaffle Roland R Sävendahl Lars L Sommer Grit G Thomas Muriel M Tidblad Anders A Tollerfield Sally S Van Eycken Liesbet L Zandwijken Gladys R J GRJ

The Journal of clinical endocrinology and metabolism 20170501 5

<h4>Context</h4>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.<h4>Objective</h4>To examine cancer risks in relation to GH treatment.<h4>Design</h4>Cohort study.<h4>Setting</h4>Population-based.<h4>Patients</h4>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-s ...[more]

PMID: 28187225

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Project description:BackgroundSince recombinant human growth hormone (rhGH) became available in 1985, the spectrum of indications has broadened and the number of treated patients increased. However, long-term health-related quality of life (HRQoL) after childhood rhGH treatment has rarely been documented. We assessed HRQoL and its determinants in young adults treated with rhGH during childhood.Methodology/principal findingsFor this study, we retrospectively identified former rhGH patients in 11 centers of paediatric endocrinology, including university hospitals and private practices. We sent a questionnaire to all patients treated with rhGH for any diagnosis, who were older than 18 years, and who resided in Switzerland at time of the survey. Three hundred participants (58% of 514 eligible) returned the questionnaire. Mean age was 23 years; 56% were women; 43% had isolated growth hormone deficiency, or idiopathic short stature; 43% had associated diseases or syndromes, and 14% had growth hormone deficiency after childhood cancer. Swiss siblings of childhood cancer survivors and the German norm population served as comparison groups. HRQoL was assessed using the Short Form-36. We found that the Physical Component Summary of healthy patients with isolated growth hormone deficiency or idiopathic short stature resembled that of the control group (53.8 vs. 54.9). Patients with associated diseases or syndromes scored slightly lower (52.5), and former cancer patients scored lowest (42.6). The Mental Component Summary was similar for all groups. Lower Physical Component Summary was associated with lower educational level (coeff. -1.9). Final height was not associated with HRQoL.Conclusions/significanceIn conclusion, HRQoL after treatment with rhGH in childhood depended mainly on the underlying indication for rhGH treatment. Patients with isolated growth hormone deficiency/idiopathic short stature or patients with associated diseases or syndromes had HRQoL comparable to peers. Patients with growth hormone deficiency after childhood cancer were at high risk for lower HRQoL. This reflects the general impaired health of this vulnerable group, which needs long-term follow-up.

Project description:BackgroundPrevious research suggests exposure to nicotine replacement therapy (NRT) may be associated with an increased risk of cardiovascular disease (CVD).MethodsUsing data from the United Kingdom's Clinical Practice Research Datalink, this study aimed to evaluate CVD events and survival among individuals who attempted smoking cessation with the support of NRT compared with those aided by smoking cessation advice only. We studied CVD outcomes over 4 and 52 weeks in 50,214 smokers attempting to quit - 33,476 supported by smoking cessation advice and 16,738 with the support of NRT prescribed by their primary care physician. Patients were matched (2 smoking cessation advice patients:1 NRT patient) on demographic and clinical characteristics during a baseline year preceding their quit attempt. Cox proportional hazard regression, conditional negative binomial regression model, and conditional logistic regression were used to analyze data.ResultsMean (standard deviation) population age was 47 (11.2) years; 51% were females. Time to first diagnosis of ischemic heart disease (IHD) among NRT and smoking cessation advice patients was similar within the first 4 weeks, but shorter for NRT patients over 52 weeks (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.03-1.77). A similar trend was observed for cerebrovascular disease (HR: 1.54, 95% CI: 1.08-2.19). NRT patients with a prior diagnosis of IHD or cerebrovascular disease had a higher rate of primary or secondary care consultations for IHD or cerebrovascular disease by 52 weeks (rate ratio: 1.50, 95% CI: 1.14-1.99). Patients prescribed NRT had a shorter survival time over 52 weeks, compared with those receiving advice only (HR: 1.39, 95% CI: 1.09-1.76).ConclusionOur findings suggest that treatment with NRT over 4 weeks does not appear to have an impact on cardiovascular risks. However, a longer follow-up period of 52 weeks resulted in an increase in cardiovascular events for patients prescribed NRT, compared with those receiving smoking cessation advice only.

Project description:IntroductionChildhood cancer and its treatment may lead to various health complications. Related impairment in quality of life, excess in deaths and accumulated healthcare costs are relevant. Genetic variations are suggested to contribute to the wide inter-individual variability of complications but have been used only rarely to risk-stratify treatment and follow-up care. This study aims to identify germline genetic variants associated with acute and late complications of childhood cancer.Methods and analysisThe Genetic Risks for Childhood Cancer Complications Switzerland (GECCOS) study is a nationwide cohort study. Eligible are patients and survivors who were diagnosed with childhood cancers or Langerhans cell histiocytosis before age 21 years, were registered in the Swiss Childhood Cancer Registry (SCCR) since 1976 and have consented to the Paediatric Biobank for Research in Haematology and Oncology, Geneva, host of the national Germline DNA Biobank Switzerland for Childhood Cancer and Blood Disorders (BISKIDS).GECCOS uses demographic and clinical data from the SCCR and the associated Swiss Childhood Cancer Survivor Study. Clinical outcome data consists of organ function testing, health conditions diagnosed by physicians, second primary neoplasms and self-reported information from participants. Germline genetic samples and sequencing data are collected in BISKIDS. We will perform association analyses using primarily whole-exome or whole-genome sequencing to identify genetic variants associated with specified health conditions. We will use clustering and machine-learning techniques and assess multiple health conditions in different models.DiscussionGECCOS will improve knowledge of germline genetic variants associated with childhood cancer-associated health conditions and help to further individualise cancer treatment and follow-up care, potentially resulting in improved efficacy and reduced side effects.Ethics and disseminationThe Geneva Cantonal Commission for Research Ethics has approved the GECCOS study.Research findings will be disseminated through national and international conferences, publications in peer-reviewed journals and in lay language online.Trial registration numberNCT04702321.

Dataset Information

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

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

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