Evidence from MHT use suggests that more exposure to oestrogen reduces risk of CRC.3, 4, 13 Estrogen exerts its effects in colon cells predominantly through the nuclear receptor oestrogen-receptor β (ERβ),14, 15 which has mainly anti-proliferative effects16 and its expression is inversely related to cancer stage, tumour extent, and mortality.17, 18 Longer use of MHT appears to be associated with high ERβ expression in tumours.19 If similar mechanisms hold then longer endogenous oestrogen exposure (through earlier age at menarche and/or later age at menopause) would reduce CRC risk as well. This evidence concerns the gene ESR2 and cancer.