IGFBP3 and colorectal cancer: Therefore, to increase statistical efficiency, we created another binary variable combining molar IGF-1/IGFBP-3 ratio and C-peptide levels (0 =  molar IGF-1/IGFBP-3 ratio below median and C-peptide below median; 1 =  molar IGF-1/IGFBP-3 ratio above or equal to median or C-peptide above or equal to median) and examined additive and multiplicative interactions between this combined variable and plasma 25(OH)D levels (above or equal median vs. below median) with regard to colorectal cancer risk (Figure 2).