Recent MR studies have shown that genetically predicted testosterone and IGF-1 are both associated with a higher risk of breast cancer,20,30 and that genetically predicted SHBG is associated with a lower risk of breast cancer;31 it should be noted, however, that these genetic associations may not demonstrate direct causal effects, since testosterone might affect risk by acting as a precursor of oestradiol, and SHBG probably affects risk by regulating the bioavailability of sex hormones. This evidence concerns the gene IGF1 and breast cancer.