Supporting the idea of these direct effects, metformin reportedly potentiated the effect of neoadjuvant chemotherapy in early-stage breast cancer [87], decreased the risk of colorectal cancer in a small randomized trial involving non-diabetic subjects [88], and was associated with a decreased cancer risk while another insulin-sensitizer, thiazolidinedione, were not [18], [54], [89], [90]. This evidence concerns the gene INS and colorectal cancer.