Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959–85: a cohort study

Summary

Background

Growth hormone raises serum concentrations of insulin-like growth factor IGF-I, which is mitogenic and antiapoptotic. There is evidence that raised endogenous levels of growth hormone and IGF-I might be associated with increased risk of certain solid cancers, but there have been no data on long-term risks of solid cancers after growth hormone treatment.

Methods

We did a cohort study to investigate cancer incidence and mortality in 1848 patients in the UK who were treated during childhood and early adulthood with human pituitary growth hormone during the period from 1959 to 1985. Patients were followed up for cancer incidence to December, 1995 and for mortality to December, 2000. Risk of cancer in the cohort was compared with that in the general population, controlling for age, sex, and calendar period.

Findings

Patients treated with human pituitary growth hormone had significantly raised risks of mortality from cancer overall (standardised mortality ratio 2·8, 95% CI 1·3–5·1; ten cases), colorectal cancer (10·8, 1·3–38·8; two cases), and Hodgkin's disease (11·4, 1·4–41·3; two cases). Incidence of colorectal cancer was also greatly raised (7·9, 1·0–28·7). After exclusion of patients whose original diagnosis rendered them at high risk of cancer, the significance and size of the risks of colorectal cancer incidence and mortality, and of Hodgkin's disease mortality were increased.

Interpretation

Although based on small numbers, the risk of colorectal cancer is of some concern and further investigation in other cohorts is needed. We have no evidence as to whether growth hormone in modern dosage regimens is associated with an increased risk of colorectal cancer.

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.