Cancer risks in patients treated with growth hormone in childhood: the SAGhE European cohort study

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: The cohort comprised 23,984 patients treated with recombinant GH (r-hGH) in 8 European countries since this treatment was first used in 1984. Cancer expectations were 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 (standardised incidence ratio 2.8 (95% confidence interval 1.1-7.5) and bladder (16.3 (5.2-50.4)) 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, risk of cancer mortality increased significantly with increasing daily r-hGH dose (p trend<0.001). Hodgkin lymphoma 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 Hodgkin lymphoma risks, need further investigation.