Reduced mammary gland carcinogenesis in transgenic mice expressing a growth hormone antagonist

Several reports have provided evidence that body size early in life is posi tively correlated with risk of subsequent breast cancer, but the biological basis for this relationship is unclear. We examined tumour incidence in tr ansgenic mice expressing a growth hormone (GH) antagonist and in non-transg enic littermates following exposure to dimethylbenz[a]anthracene (DMBA), a well characterized murine mammary gland carcinogen. The transgenic animals had lower IGF-I levels, were smaller in terms of body size and weight, and exhibited decreased tumour incidence relative to controls. The demonstratio n that both body size early in life and breast cancer incidence are influen ced by experimental perturbation of the GH-IGF-I axis in a transgenic model provides evidence that variability between individuals with respect to the se hormones underlies the relationship between body size early in life and breast cancer risk observed in epidemiological studies. (C) 2001 Cancer Res earch Campaign.