Letter: Negligible risk

From Paul Schofield, University of Cambridge and Ben Mepham, University of Nottingham

In a response to our letter of 10 September, Samuel Epstein (Letters, 29 October) alleges that we are not aware of evidence suggesting a link between IGF-1 and breast cancer. The matter is of interest in relation to suggestions that levels of IGF-1 may be higher than normal in milk from cows injected with the growth hormone, bovine somatotropin.

However, contrary to Epstein’s contention, there is no evidence that IGF-1 can cause neoplastic transformation in any cell type. Evidence does suggest that, in vitro, selected breast carcinoma cell lines are dependent on either exogenous or endogenously produced IGF-1, but they share this property with countless other normal and abnormal cell types. It is true that IGF-1 is permissive for expression of other transforming mutations, but again this is usually a general requirement for cell growth.

There is conflicting evidence as to whether the acquisition of breast epithelial cells of the ability to synthesise IGF-1 is rate limiting in breast tumourigenesis; the only consistent conclusion is that production of paracrine IGF-1 by the surrounding normal stromal tissue of the breast may contribute to the continued growth of tumours. It is important to draw the distinction between circulating and locally produced IGF-1.

If Epstein is correct, an increase in the incidence of breast cancer should be evident in clinical and experimental conditions where circulating levels of IGF-1 are elevated. The generation of transgenic mice carrying an overexpressed IGF-1 gene, provides no evidence for increased breast tumour incidence, despite somatic overgrowth and high levels of circulating IGF-1. Acromegalic humans similarly have greatly elevated bioactive serum IGF-1, yet have no significantly increased incidence of breast cancer.

By emphasising a negligible risk, Epstein diverts attention from potential effects of milk borne IGF-1 in the gut, an important safety issue, which we believe should be addressed as a matter of urgency.