Considering previous findings from the NHS blood cohort which suggested that among women with high IGF-1/IGFBP-3 ratio having also high C-peptide levels did not further increase risk of colorectal cancer and vice versa [62], we examined associations between different combinations of molar IGF-1/IGFBP-3 ratio and C-peptide and plasma 25(OH)D and risk of colorectal cancers using our combined HPFS and NHS dataset. The gene discussed is IGFBP3; the disease is colorectal cancer.