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Raised Cancer Risk From Human Growth Hormone Treatment

An increase in cancer incidence compared with the general population has been found among British men and women given human pituitary growth hormone up to the mid 1980s.

Dr. Anthony Swerdlow and colleagues at the Institute of Cancer Research, and Institute of Child Health, Sutton, Surrey, England, caution that the cases they found are small in number and there is no indication that growth hormone in modern dosage regimens is associated with an increased risk.

At the same time, they declare: "Our data do not show conclusively whether cancer incidence is increased by growth hormone treatment, but they do suggest the need for increased awareness of the possibility of cancer risks, and for surveillance of growth hormone-treated patients."

Human pituitary growth hormone was first used to counteract short stature in children and young adults, but the advent of synthetic growth hormone has replaced human growth hormone therapy.

The role of growth hormone in carcinogenesis is not clear, the researchers point out, but it raises serum concentrations of insulin-like growth factor (IGF)-I, which is mitogenic and antiapoptotic. Both in-vitro and animal studies suggest that growth hormone might raise the risk of hyperplasia and malignancy.

Dr. Swerdlow and colleagues investigated cancer incidence and death in 1,848 British men and women who were treated during childhood and early adulthood with human pituitary growth hormone between 1959 and 1985. The risk of cancer in the study population was compared with that in the general population, controlling for age and sex.

Although the overall number of patients who developed cancer was small (10 cases), it represented a significantly higher risk of mortality from cancer according to standardized mortality ratios. After the exclusion of patients whose reason for growth hormone treatment rendered them at a high risk of cancer, the risk of incidence of colorectal cancer was significant, as were the risks of death from colorectal cancer or Hodgkin's disease.

Concern about cancer in patients treated with growth hormone has focused primarily on risk of leukemia, but no leukemia cases occurred after treatment among the cohort. "Our finding adds to evidence from other cohort studies which suggest that leukemia risk is not substantially raised if high-risk groups such as those with chromosomal fragility are excluded."

Dr Swerdlow and colleagues said there has been much less research on other cancer risks, and their findings are not reassuring. Despite the limitations in their study "the high incidence of cancer, and in particular of colon cancer, is worrying."

Frequency of colon cancer mortality after growth hormone treatment was raised. The number of cases was small, but is of concern because it concurs with raised risks found in patients with acromegaly and in individuals with previously increased concentrations of IGF-I.

Because of the large relative risk and supporting evidence, there is an urgent need to obtain further data, they conclude
Lancet 2002; 360: 273-77.

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