ArticlesRisk of cancer in patients treated with human pituitary growth hormone in the UK, 1959–85: a cohort study
Introduction
Treatment of patients with growth hormone was initially used to remedy short stature in childhood.1 However, as experience with, and availability of, the treatment improved, the range of indications and the number of patients for which growth hormone was prescribed increased greatly. This increase was especially noticeable after synthetic growth hormone became available in 1985. The role of growth hormone in carcinogenesis is unclear, but it raises serum concentrations of insulin-like growth factor (IGF)-I, which is mitogenic and antiapoptotic, and results from in-vitro and animal studies suggest that growth hormone might raise the risk of hyperplasia and malignancy.2, 3 Furthermore, there is epidemiological evidence that the growth hormone/IGF-I axis might affect cancer risk in human beings. Results of cohort studies suggest,4, 5, 6, 7, 8 although not entirely consistently,9 that raised concentrations of IGF-I in serum predict a greater risk of certain cancers, and there is evidence that the risk of colonic polyps and colon cancer are increased in patients with acromegaly,10, 11, 12, 13 a disorder attributable to endogenous excess of growth hormone.
Direct evidence about cancer risk in patients treated with growth hormone is very limited. Studies of leukaemia after childhood growth hormone treatment14, 15, 16, 17 have found a raised risk in patients overall.14, 16, 17 However, several cases were in patients with an underlying high risk (eg, Fanconi's anaemia) and after exclusion of these high risk conditions, risk does not seem to be substantially raised, if at all. There are no reported data on long-term risks of solid malignancies; the only analyses have been after an average of 4 years since first treatment.18 We therefore examined risk of malignant neoplasms in patients in the UK who were treated with human pituitary growth hormone before its use was discontinued in May, 1985, and for whom there is now up to 40 years of follow-up.
Section snippets
Methods
Treatment with human pituitary growth hormone in the UK started in 1959 as a Medical Research Council clinical trial, and when this trial ended in 1977, treatment was continued as a health service activity administered by a central committee. Treatment of each new patient had to be authorised centrally, and the end of treatment reported to the central authority, whereon supplies of growth hormone for the patient were stopped.
After approval from the Great Ormond Street Hospital and Institute of
Results
We identified 1849 UK residents who had been treated with human growth hormone as part of the national scheme between 1959 and 1985. Because this scheme was centrally administered and controlled, and also because data from many different sources were used, we are confident that we have identified all patients treated under the national scheme. We were able to ascertain the commencement date of growth hormone treatment for all patients, and definite end dates of treatment for all but ten
Discussion
Concern about cancer in patients treated with growth hormone has focused primarily on risk of leukaemia, perhaps because available data have largely been for children, in whom leukaemia is the most common cancer. No leukaemias occurred after treatment in our cohort; we calculated an expected incidence of 0·71. Our finding adds to evidence from other cohort studies14, 16, 17 which suggest that leukaemia risk is not substantially raised if high-risk groups such as those with chromosomal fragility
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