For example, expression of the GH gene in breast epithelial cells is associated with the presence of proliferative disorders of the mammary gland;15 the GH receptor (GHR) gene has higher expression in breast tumors compared to adjacent normal breast tissue;16 and deficiency of GHR due to splice and nonsense mutations in the GHR gene results in a drastic reduction of risk of any type of cancer.17 Leptin (LEP) signaling also interacts with the insulin/IGF-1 system and may affect risk of breast cancer. This evidence concerns the gene IGF1 and breast carcinoma.